10-Methoxy-Harmalan - liquid product for R&D

[haidut]

The chemical has already been discussed in another thread (see 1st link in References below), so this is just the announcement that it is now available for purchase.

The units listed on the label are just for measurement purposes. They do not indicate or suggest optimal dose. Please note that similar to the products sold by companies like BlueSky, this product if for lab/research use only. The product can be ordered from the link below:
http://www.idealabsdc.com/lab

*******************************************************************************
A naturally occurring (e.g. in tobacco) β-carboline derivative, 10-methoxy-harmalan (10-MeO-Harmalan) has been shown to act as a serotonin antagonist both in-vitro and in-vivo, with a mechanism and potency similar to the ergot derivatives, but without their psychotropic/hallucinogenic effects. In addition, several studies suggest dopaminergic effects of most naturally occurring β-carbolines. The chemical is currently not known to be regulated/restricted and is available commercially from a number of major chemical vendors.

Drops per container: about 250
Each drop contains the following ingredients:

10-MeO-Harmalan: 100 mcg

Other ingredients: add product to shopping cart to see info
*******************************************************************************

References:

10-methoxy-harmalan ,an anti-serotonin chemical?

Danny roddy and georgi dinkov discussed 10-methoxy-harmalan on the latest podcast ,which seems to be as anti-serotonin as LSD ,but without any hallucination effects . Anybody heard of it or knows where to get it? Let's compile some info!

raypeatforum.com

Harman and norharman, metabolites of the entomopathogenic fungus Conidiobolus coronatus (Entomophthorales), affect the serotonin levels and phagocytic activity of hemocytes, insect immunocompetent cells, in Galleria mellonella (Lepidoptera) - Cell &

Background Although the β-carboline alkaloids harman and norharman are considered as plant metabolites, they can also be secreted by fungi such as the entomopathogen Conidiobolus coronatus. Norharman and harman are also known to be reversible competitive monamine oxidase inhibitors, which...

cellandbioscience.biomedcentral.com

"...A common feature of the immune cells of mammals and insects is the occurrence of serotonin receptors. Qi et al. [15] identified 5-HT1B, 5-HT2B, and 5-HT7 receptor expression in naive insect hemocytes, but only 5-HT1B and 5-HT2B appeared to have functional roles. While blockade of 5-HT1B significantly reduced phagocytic ability, blockade of 5-HT2B increased hemocyte phagocytosis. Harman and norharman are antagonists of both type 5-HT1 and 5-HT2 serotonin receptors,.."

Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-β-carboline: a new anti-Parkinson drug? - PubMed

β-carbolines are potential endogenous and exogenous neurotoxins that may contribute to the pathogenesis of Parkinson's disease (PD). 9-methyl-β-carboline exhibits multimodal effects that could be beneficial in the treatment of PD. It shows stimulatory effects to dopaminergic neurons by...

pubmed.ncbi.nlm.nih.gov

9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes - PubMed

β-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of...

pubmed.ncbi.nlm.nih.gov

Error - Cookies Turned Off

onlinelibrary.wiley.com

Identification and occurrence of beta-carboline alkaloids in raisins and inhibition of monoamine oxidase (MAO) - PubMed

Monoamine oxidase (MAO) is a mitochondrial enzyme involved in the oxidative catabolism of neurotransmitters and xenobiotic amines, including vasopressor and neurotoxic amines, and a current target for antidepressant and neuroprotective drugs. Raisin extracts and homogenates exhibited reversible...

pubmed.ncbi.nlm.nih.gov

Interaction of β-carbolines with central dopaminergic transmission in mice: structure-activity relationships

Although several β-carboline alkaloids display hallucinogenic properties in humans, their mechanism of action remains unclear. To ascertain their infl…

www.sciencedirect.com

Harmane and harmalan are bioactive components of classical clonidine-displacing substance - PubMed

Elucidation of the structure of the endogenous ligand(s) for imidazoline binding sites, clonidine-displacing substance (CDS), has been a major goal for many years. Crude CDS from bovine lung was purified by reverse-phase high-pressure liquid chromatography. Electrospray mass spectrometry (ESMS)...

pubmed.ncbi.nlm.nih.gov

 

[LuMonty]

I've been looking forward to this and just ordered. I saw that you had trialed it, Haidut. In your experience, how would you say it differs from lisuride or metergoline?

 

[Mauritio]

The chemical has already been discussed in another thread (see link in References below), so this is just the announcement that it is now available for purchase.

The units listed on the label are just for measurement purposes. They do not indicate or suggest optimal dose. Please note that similar to the products sold by companies like BlueSky, this product if for lab/research use only. The product can be ordered from the link below:
http://www.idealabsdc.com/lab

*******************************************************************************
A naturally occurring (e.g. in tobacco) β-carboline derivative, 10-methoxy-harmalan (10-MeO-Harmalan) has been shown to act as a serotonin antagonist both in-vitro and in-vivo, with a mechanism and potency similar to the ergot derivatives, but without their psychotropic/hallucinogenic effects. The chemical is currently not known to be regulated/restricted and is available commercially from a number of major chemical vendors.

Drops per container: about 250
Each drop contains the following ingredients:

10-MeO-Harmalan: 100 mcg

Other ingredients: add product to shopping cart to see info
*******************************************************************************

References:

10-methoxy-harmalan ,an anti-serotonin chemical?

Danny roddy and georgi dinkov discussed 10-methoxy-harmalan on the latest podcast ,which seems to be as anti-serotonin as LSD ,but without any hallucination effects . Anybody heard of it or knows where to get it? Let's compile some info!

raypeatforum.com

MUCH anticipated haha

A few questions:

1. Do you know which specific serotonin or dopamine receptors it binds to ? Any affinity for dopamine receptors, at all ?

2. I've read that 10-methoxy-harmalan is a MAO-A inhibtor . Any info on that?

 

[dhtsupreme]

@haidut On a separate thread you detailed your experience of its effects. Did you use it topically? And if so on the navel or somewhere else?

 

[Mauritio]

Here are the existing reviews:

So, just a few quick comments. I have already tried 10-methoxyharmalan (10-MH) myself, and and off for a few months. The anti-serotonin effects are quite pronounced and can be felt at doses as low as 100mcg. This basically matches what the study on 10-MH serotonin antagonism found, as LSD is used clinically in doses of around 200mcg-400mcg daily but such doses are used to induce hallucinations. The anti-serotonin effects of LSD manifest even at doses as low as 50mcg, which is something studies with the closely related chemical lisuride also confirmed - i.e. while lisuride is used clinically in doses around 200mcg, doses in the 50mcg range still powerfully lower prolactin, while avoiding issues such as nausea and hypotension commonly seen with those chemicals. So, if 10-MH works similar to LSD but need 2-fold higher doses to produce the same effects, this means 100mcg should be able to match the effects of 50mcg lisuride but without the nausea, dizziness, etc. That is basically what I experienced when trying it.
The anti-serotonin effects (clear vision, stress-free digestion (even of starch), improved mood/cognition, relaxation, etc) of a single 200mcg dose of 10-MH usually last up to a day for me. Nausea does not seem to occur unless doses >1mg are reached but such high doses are quite unnecessary IMO as 100mcg-200mcg work quite well. I have tried up to 5mg as single doses and there are NO hallucinations, at least for me. Btw, despite LSD having a unique reputation as hallucinogen, virtually all ergot derivatives can cause hallucinations (and tremors) if used in high doses and/or for extended periods of time.
We have already started work on synthesizing it, so if the process is efficient and produces decent outputs, we should be able to release it in a month or so. We don't know yet if this would be commercially feasible. The papers listing its synthesis routes claim it should be relatively easy 1-2 step process but we have encountered several times in the past that published synthesis routes do not actually work as described. So, there is a good chance we will release this, but it is not guaranteed until we confirm the synthesis is possible and affordable (both in materials and manpower). In the meantime, you can get it from Sigma or other vendors selling it. I have not seen any indication that it is a controlled chemical in any country and all chemical vendors that sell it, do so without any restrictions or requiring any licenses.
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. Finally, 10-MH is structurally very similar to the 5-HT3 antagonist ondansetron, which IMO corroborates its effects as a serotonin antagonist, especially considering that the initial idea for developing ondansetron came precisely from work with the beta-carbolines / alkaloids like harmine, harmaline, and harmalan.

Ondansetron - Wikipedia

en.wikipedia.org

Also, the optimal doses of ondansetron for systemic health seem to be in the 0.5mg-1mg daily range (based on animal studies, and despite its clinical usage in 4mg doses) and this is what Ray has also been suggesting to people in regards to ondansetron dosing. So, the optimal dosing for 10-MH is probably in that same range (0,5mg-1mg daily), but in my experience even 100mcg daily produces noticeable anti-serotonin effects.


@Drareg @James b @Mauritio @MeatOrchid @Waynish @jmojo

I’m finding this quite androgenic, I’ve been using 300mcg, I never really noticed this with lisuride, metergoline or cypro.
There are no noticeable side effects at these dosages for 2 weeks, I may up the dose for science, how were you at 5mg?
I may try 1mg for a bit just to see but 300 mcg is highly effective.

I will venture a guess that 6-MEO harmalan doesn’t inhibit MAO-A in low dosages, I know harmaline does inhibit MAO-A, for example I’m very sensitive to methylene blue because of this, if I take a few hundred mcg of methylene blue for a few days I notice increased serotonin like symptoms, I can take 1 drop of oxidation occasionally and it’s beneficial but that’s it for me.

And on this thread they discus 10MH as possible (and apparently very effective) treatment for Parkinson's.

6 methoxy harmalan might very well cure/reverse parkinsons . At least the testimonials are very promising.


View: https://www.reddit.com/r/ivermectin/comments/oxen8i/dr_malone_claims_that_physicians_in_spain_are/h7m8thu?utm_medium=android_app&utm_source=share&context=3

 

[haidut]

I've been looking forward to this and just ordered. I saw that you had trialed it, Haidut. In your experience, how would you say it differs from lisuride or metergoline?

The overall effects on digestion, mood, etc are similar but I don't get nausea from 10-MH, which I do sometimes get from lisuride or metergoline.

 

[haidut]

MUCH anticipated haha

A few questions:

1. Do you know which specific serotonin or dopamine receptors it binds to ? Any affinity for dopamine receptors, at all ?

2. I've read that 10-methoxy-harmalan is a MAO-A inhibtor . Any info on that?

1. Judging from the closely related chemical below, it seems there is antagonism on 5-HT1 and 5-HT2, with possible agonism on D2.

6-MeO-THH - Wikipedia

en.wikipedia.org

"...Studies in rats have shown it to bind to a number of serotonin 5-HT1 receptors and 5-HT2 receptors, dopamine D2 receptors, benzodiazepine receptors, and imidazoline receptors.[2][3][4]"

2. I don't find it to have MAO-A inhibiting effects. Some of the studies I saw on beta-carbolines concluded that if there is any MAO inhibition it is more likely on MAO-B instead of MAO-A.

 

[Mauritio]

1. Judging from the closely related chemical below, it seems there is antagonism on 5-HT1 and 5-HT2, with possible agonism on D2.

6-MeO-THH - Wikipedia

en.wikipedia.org

"...Studies in rats have shown it to bind to a number of serotonin 5-HT1 receptors and 5-HT2 receptors, dopamine D2 receptors, benzodiazepine receptors, and imidazoline receptors.[2][3][4]"

2. I don't find it to have MAO-A inhibiting effects. Some of the studies I saw on beta-carbolines concluded that if there is any MAO inhibition it is more likely on MAO-B instead of MAO-A.

If it is an effective D2 agonsit, that would be awesome. D2 agonism is responsible for increasing insulin sensitivity, lowering prolactin and increasing social status .


They all seem to inhibit MAO-A alot more than MAO-B , although I don't know if the MAO-A inhibition is significant for 10MH in the amounts we ingest.

"Whereas there was a greater than 10,000-fold difference in potency between the action of harmaline on MAO A and MAO B, with harmane the difference was only about ten-fold. Harmaline was by far the most potent MAO A inhibitor but harmane has the most powerful action on MAO B, with an Is0 of-about 5 x 10 -6 M. THBC and 6-MeOTHBC were less potent inhibitors of both MAO A and B than harmane."

 

[johnwester130]

this looks interesting

 

[conrad0602]

Would there be any issue using this along side methylene blue?

 

[Charger]

Ordered. Looking forward to this and hopefully Cinanserin soon.

 

[haidut]

Would there be any issue using this along side methylene blue?

We can't comment on using this specific product in humans, as it is sold as a lab chemical, but considering the possibility of MOA-A inhibition mentioned above it is probably better to not mix methylene blue and generic 10-methoxy-harmalan.

 

[haidut]

If it is an effective D2 agonsit, that would be awesome. D2 agonism is responsible for increasing insulin sensitivity, lowering prolactin and increasing social status .


They all seem to inhibit MAO-A alot more than MAO-B , although I don't know if the MAO-A inhibition is significant for 10MH in the amounts we ingest.

"Whereas there was a greater than 10,000-fold difference in potency between the action of harmaline on MAO A and MAO B, with harmane the difference was only about ten-fold. Harmaline was by far the most potent MAO A inhibitor but harmane has the most powerful action on MAO B, with an Is0 of-about 5 x 10 -6 M. THBC and 6-MeOTHBC were less potent inhibitors of both MAO A and B than harmane."

View attachment 29756
View attachment 29757

Yes, I have seen that study. However, the situation in-vivo seems to be such that the over all effect of most beta-carbolines is pro-dopamine (see last link below).

Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-β-carboline: a new anti-Parkinson drug? - PubMed

β-carbolines are potential endogenous and exogenous neurotoxins that may contribute to the pathogenesis of Parkinson's disease (PD). 9-methyl-β-carboline exhibits multimodal effects that could be beneficial in the treatment of PD. It shows stimulatory effects to dopaminergic neurons by...

pubmed.ncbi.nlm.nih.gov

9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes - PubMed

β-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of...

pubmed.ncbi.nlm.nih.gov

Error - Cookies Turned Off

onlinelibrary.wiley.com

Identification and occurrence of beta-carboline alkaloids in raisins and inhibition of monoamine oxidase (MAO) - PubMed

Monoamine oxidase (MAO) is a mitochondrial enzyme involved in the oxidative catabolism of neurotransmitters and xenobiotic amines, including vasopressor and neurotoxic amines, and a current target for antidepressant and neuroprotective drugs. Raisin extracts and homogenates exhibited reversible...

pubmed.ncbi.nlm.nih.gov

Interaction of β-carbolines with central dopaminergic transmission in mice: structure-activity relationships

Although several β-carboline alkaloids display hallucinogenic properties in humans, their mechanism of action remains unclear. To ascertain their infl…

www.sciencedirect.com

 

[iso1]

Which delivery method is safer for uk ? DPD ? or doesnt matter ? Would i have to pay customs charges as well ? Also, have anybody ever 3d lab tested the stuff that is sold on idealabs ?

 

[aadrock]

Which delivery method is safer for uk ? DPD ? or doesnt matter ? Also, have anybody ever 3d lab tested the stuff that is sold on idealabs ?

Yeh lab tested pansterone on the balls. 100% purity haha

 

[iso1]

And harmaline seems to be serotonergic, so how would 10-MeO-Harmalan be the opposite ? And b-carbolines harman and norharman seems to be serotonergic as well ?

Harman and norharman, metabolites of the entomopathogenic fungus Conidiobolus coronatus (Entomophthorales), affect the serotonin levels and phagocytic activity of hemocytes, insect immunocompetent cells, in Galleria mellonella (Lepidoptera) - Cell &

Background Although the β-carboline alkaloids harman and norharman are considered as plant metabolites, they can also be secreted by fungi such as the entomopathogen Conidiobolus coronatus. Norharman and harman are also known to be reversible competitive monamine oxidase inhibitors, which...

cellandbioscience.biomedcentral.com

 

[haidut]

And harmaline seems to be serotonergic, so how would 10-MeO-Harmalan be the opposite ? And b-carbolines harman and norharman seems to be serotonergic as well ?

Harman and norharman, metabolites of the entomopathogenic fungus Conidiobolus coronatus (Entomophthorales), affect the serotonin levels and phagocytic activity of hemocytes, insect immunocompetent cells, in Galleria mellonella (Lepidoptera) - Cell &

Background Although the β-carboline alkaloids harman and norharman are considered as plant metabolites, they can also be secreted by fungi such as the entomopathogen Conidiobolus coronatus. Norharman and harman are also known to be reversible competitive monamine oxidase inhibitors, which...

cellandbioscience.biomedcentral.com

They actually state in that study you linked to that harman and norharman are antagonists on 5-HT1 and 5-HT2. The rise in serotonin is explained by the inhibition of MAO-A, for which concentrations in the micromolar range seem to be needed - higher than what is needed for serotonin receptor antagonism.
"...A common feature of the immune cells of mammals and insects is the occurrence of serotonin receptors. Qi et al. [15] identified 5-HT1B, 5-HT2B, and 5-HT7 receptor expression in naive insect hemocytes, but only 5-HT1B and 5-HT2B appeared to have functional roles. While blockade of 5-HT1B significantly reduced phagocytic ability, blockade of 5-HT2B increased hemocyte phagocytosis. Harman and norharman are antagonists of both type 5-HT1 and 5-HT2 serotonin receptors, and both increase serotonin levels by acting as MAO inhibitors. This may explain our present findings, which show that harman and norharman administration results in an increase of 5-HT in the hemolymph and elevated phagocytic activity by hemocytes."

This is corroborated by another study below that tested specifically 10-MeO-Harmalan (6-MeO-Harmalan in the picture) and found that micromolar concentrations are needed to inhibit MAO-A. In contrast, the first study in the original post showed that serotonin receptor antagonism occurred at doses about 2-fold higher than LSD, which is used in microgram amounts, which achieve low-nanomolar concentrations in-vivo. So, roughly a factor of 1,000 as a buffer/preferentiality.

https://chacruna.net/wp-content/uploads/2019/08/McKenna_et_al_Monoamine_Inhibitors_Tryptamine_Ayahuasca_Journal_Ethnopharmacology_1984.pdf

@Mauritio

 

[iso1]

@haidut ok i have genuine question, how would somebody know that research chemicals you are selling are legit ? It can be anything in the vial that possess similar properties and that would be easier for you to get and sell. How do you know that 10-MeO-Harmalan won't lose it's potency over time in the vehicle you are using. Just a healthy skepticism.

 

[haidut]

@haidut ok i have genuine question, how would somebody know that research chemicals you are selling are legit ? It can be anything in the vial that possess similar properties and that would be easier for you to get and sell. How do you know that 10-MeO-Harmalan won't lose it's potency over time in the vehicle you are using. Just a healthy skepticism.

Legit questions indeed. A relatively cheap method would be to buy a genuine sample from a legit vendor like Sigma.

https://www.sigmaaldrich.com/US/en/product/aldrich/m1626?context=product

Dissolve it in ethanol and then compare with ours. You will see identical color, taste, etc. I can also provide a COA, but of course that does not prove anything as it is coming from the claimant (me) and can be easily fabricated. So, direct personal comparison with a legit sample is the only cheap-ish method and, of course, paying for a lab independent lab analysis is the ultimate verification. Those analyses are not cheap though, but I have always encouraged people to run such tests if they can find an affordable lab.
As far as stability - also a fair point. All chemicals degrade over time, but considering ethanol is an excellent preservative, and that beta-carbolines can remain stable in things like tobacco leaves for decades (maybe even centuries, based on archeological findings of in Central America), there is a good chance the chemical will stay largely intact over the course of a few months to a year. I mean, the same concern applies to all liquid products sold by any other vendor like Amazon, and the feedback on them and the Consumer Reports tests on select products do not seem to show much in terms of degradation over the course of 3-6 months. Of course, like anything else in this life (except death and taxes) - no guarantees, claimed or implied

 

[joshquintanilla]

At long last!!

I’m wondering if this is a replacement to the other anti-serotonin chemicals due to how strong its effects are or is it to be used in conjunction with the others since some benefits might not overlap? How might this be incorporated optimally with everything else?