Beta Carboline MAOIs - towards a more effective e-liquid

[tceight]

snippets of info about beta carbolines,

some good,

"β-Carboline alkaloids are natural products widely distributed in plants and also found in alcoholic beverages, well-cooked foods and tobacco smoke. Various authors have reported genotoxic activities of several carboline in prokaryotic and eukaryotic cells that have been attributed to their abilities to intercalate into dna. But studies on the genotoxic and on the cytotoxic potencies in human cells in vitro are not found in the literature. In the present study the toxicities of one full aromatic β-carboline alkaloid (harmine) and one dihydro-β-carboline alkaloid (harmaline) were evaluated by means of two in vitro human cell assays: the cytochalasin-B blocked micronucleus (CBMN) assay and the viability/colony formation assay with four different human cultured non-transformed (CCD18Lu) and transformed (HeLa, C33A and SW480) cells. Neither alkaloid was able to induce micronuclei levels above that of control levels in a wide range of doses tested; although, harmine at the highest concentrations assayed induced apoptotic as well as necrotic cells. Harmine produced a good viability of all cell lines assayed (control and tumor) while harmaline significantly reduced the viability of transformed and non-transformed cell lines in a dose-dependent manner. Harmine displayed a dose-dependent inhibitory effect on cell proliferation against all human carcinoma cells, but the SW480 transformed cell line showed a higher sensitivity. These results suggested that harmine was identified as a useful inhibitor of tumor development.

and some not so good.

[FONT=Verdana,Arial,Helvetica]From the IRANIAN JOURNAL OF PHARMACOLOGY & THERAPEUTICS:

Harmine (banisterine). C13H12ON2 - It is present in P. harmala and in some species of Banisteia, viz., B. caapi, Spruce., B. lutea and B. metallicolor. The alkaloid is optically inactive and forms colorless rhombic prisms from methanol. It is slightly soluble in water, alcohol or ether. Solutions of its salts show a deep blue fluorescence. Pharmacologically, harmine resembles harmaline in its actions but is less toxic. The hydrochloride has been found to be highly active against Mycobacterium tuberculosis [7].

Harmaline (harmidine). C13H15ON2 - First isolated by Göbel [5] from the seeds and roots of P. harmala, this is the major alkaloid of this plant. It crystallizes in colorless or pale yellow prisms and is optically inactive. This compound is slightly soluble in water, alcohol and ether, quite soluble in hot alcohol and dilute acids. Its hydrochloride dihydrate, which crystallizes as yellow needles, is moderately soluble in water and alcohol. Harmaline is almost twice as toxic as harmine and in moderate doses causes tremors and clonic convulsions but with no increase in spinal reflex excitability [6]. Lethal doses bring about convulsions, which are soon followed by motor paralysis due to the marked depressive action upon the central nervous system. Respiration is paralyzed and a decrease in body temperature occurs. The perfused heart is arrested in diastolic phase and the contractions of smooth muscle are diminished with the exception of the uterus, which may be made to contract more powerfully. Over a wide range of doses there is a reduction in blood pressure due to a pronounced weakening of the heart muscle. [/FONT]

 

[tceight]

for anyone experimenting with water based extractions, remember to refrigerate!
I left out a couple of extracts for less than 24 hr's and there were mold colonies growing on them.
I hadnt intended on consuming these in any way, so no great loss, except for having to start over again.

 

[DemonCowboy]

for anyone experimenting with water based extractions, remember to refrigerate!
I left out a couple of extracts for less than 24 hr's and there were mold colonies growing on them.
I hadnt intended on consuming these in any way, so no great loss, except for having to start over again.

i'm a know-nothing - this is way over my head observer. but just watch that turns out to b part of the extraction process to get what's needed... that would b my luck after throwing it out anyway

 

[kinabaloo]

for anyone experimenting with water based extractions, remember to refrigerate!
I left out a couple of extracts for less than 24 hr's and there were mold colonies growing on them.
I hadnt intended on consuming these in any way, so no great loss, except for having to start over again.

I agree, I had also warned about this somewhere in a previous post (maybe another thread).

Suggests proteins and / or sugars / starches in the extract.

I haven't got far with my latest testing, although did find a considerable dry residue that is consistent with tanins/carbs. Included about 30% ethanol to guard against mold.

A shorter extraction time my be better in this regard (less unwanteds). But a warm and slightly acidic one to get the carbolines.

 

[tceight]

i'm a know-nothing - this is way over my head observer. but just watch that turns out to b part of the extraction process to get what's needed... that would b my luck after throwing it out anyway

That's often the way things work out for me too, especially right after I clean out the garage, the very next day I find I really did need something in that pile of junk. Do we have any mycologists here?

 

[tceight]

in looking at the various forms of alkaloids, I think I have been handcuffing myself by assuming the need for them to be in freebase form to be effective in the E-juice. I came to this assumption because there have been several posts and threads on the differences in pH as it affects nicotine absorption via either the mouth or the lungs.

Then I ran across a research article about cigar smoking, and how the pH of the smoke changes throughout the cigar from acid to alkaline, and how there was no apparent correlation in serum levels.

I've found several studies on various drugs and pH absorption differences and they generally are insignificant.
http://www.aapspharmscitech.org/articles/pt0701/pt070123/pt070123_figure2.jpg
here for example, is a graph for oxycodone shows only a slight difference in absorption between a pH of 4 and a pH of 9.

I think this common (mis)understanding originates from the notion of 'freebase' (alkaline) as it applies to illicit alkaloids, such as 'crack' is more intense than 'coc@ine' as a salt, and that somehow freebase drugs are better absorbed.

The difference is more readily and simply explained by the differences in the route of administration of the two forms, inhalation vs snorting.

in the case of Harmine, salt forms are preferential, as the salts are highly water soluble whereas the freebase form is only slightly water soluble.

 

[DemonCowboy]

That's often the way things work out for me too, especially right after I clean out the garage, the very next day I find I really did need something in that pile of junk. Do we have any mycologists here?

i figured it was possible, because i've seen the way tobacco is made - for instance they "grease" the shredding machines by throwing a green load in tobacco worms and all.

i wonder if i can find the friend that made that video or if i can find it....hmmm

but anyway if they'll treat their machines like that i bet there's mold getting on the tobacco somewhere in the process

 

[kinabaloo]

in the case of Harmine, salt forms are preferential, as the salts are highly water soluble whereas the freebase form is only slightly water soluble.

Whatever allows us to extract the wanteds from the unwanteds. The salts decompose favorably on heating. Whether biologically active or become so (freebased) in the body I don't know (this might be important to the extent that some liquid would be 'spat out' as a mist before atomiser heats up enough to cause decomposition.

Further to my previous post, on simmering the water (and some ethanol) tobacco extract, there was a noticeable caramel-like smell; could well be caramelisation, though I can't be sure. We still need a way to remove the carbs and proteins. That's the key.

Precipitating suitable salts might be the only feasible approach to achieve that end.

 

[tceight]

Whatever allows us to extract the wanteds from the unwanteds. The salts decompose favorably on heating.

Further to my previous post, on simmering the water (and some ethanol) tobacco extract, there was a noticeable caramel-like smell; could well be caramelisation, though I can't be sure. We still need a way to remove the carbs and proteins. That's the key.

regarding harmine, I was refering to water solubility for tissue absorption, not for extraction.

~~ I guess my whole point was, the potential extraction methodologies, with the goal of maintaining safe concentrations of nicotine at all times, opens exponentially when you allow the finished product to exist as salts. At least, it opened several potential doors in my mind.

 

[kinabaloo]

regarding harmine, I was refering to water solubility for tissue absorption, not for extraction.

~~ I guess my whole point was, the potential extraction methodologies, with the goal of maintaining safe concentrations of nicotine at all times, opens exponentially when you allow the finished product to exist as salts. At least, it opened several potential doors in my mind.

Indeed. If wearing gloves, there's not necessarily much danger involved.

At absorption stage, whether salt forms would be biologically active or become so (freebased) in the body I don't know (this might be important to the extent that some liquid would be 'spat out' as a mist before atomiser heats up enough to cause decomposition.

 

[kinabaloo]

Only about 1/30 as much carolines are required in comparison to nicotine. Adding a small/tiny amount of PF extract to e-liquid to give this ratio might be the easiest approach, at least for most people - assuming they can do the maths and the PF concentration in terms of carboline content is accurately known.

 

[tceight]

Indeed. If wearing gloves, there's not necessarily much danger involved.

At absorption stage, whether salt forms would be biologically active or become so (freebased) in the body I don't know (this might be important to the extent that some liquid would be 'spat out' as a mist before atomiser heats up enough to cause decomposition.

I assume if it can't be absorbed into the tissue, it can't be 'biologically active'

I disagree about the potential danger, quite strongly! especially in my house.
all it would take would be a small spill or splatter, even a drop on a counter, table or floor and kid's will find it. 100mg is a vanishingly small amount.

 

[kinabaloo]

I assume if it can't be absorbed into the tissue, it can't be 'biologically active'

I disagree about the potential danger, quite strongly! especially in my house.
all it would take would be a small spill or splatter, even a drop on a counter, table or floor and kid's will find it. 100mg is a vanishingly small amount.

Clearly needs a lot of care and thinking through in advance, careful clean-up after etc. It might well be not worth the risk.

We are left then with the alternative approach I mentioned in my post above.

 

[tceight]

Only about 1/30 as much carolines are required in comparison to nicotine. Adding a small/tiny amount of PF extract to e-liquid to give this ratio might be the easiest approach, at least for most people - assuming they can do the maths and the PF concentration in terms of carboline content is accurately known.

agree that adding 'stuff' until it works is a great and simple method, if you can find what 'stuff' to add. PF isn't the answer for many people that have tried it. I am going to do an extraction, and see if this route is adequate. I will make up a few ml of each, freebase and salts, and see if there is any difference.
At least then, I know I am heading in the right direction.

 

[kinabaloo]

Or we do enough here to show a commercial body that they could develop it, which solves that particular problem.

I think the research papers we have pointed to, the whole 'something missing' debate (which many can agree on), DVaps tests and some testing others did with PF all point to this being something a commercial body could take up.

 

[kinabaloo]

agree that adding 'stuff' until it works is a great and simple method, if you can find what 'stuff' to add. PF isn't the answer for many people that have tried it. I am going to do an extraction, and see if this route is adequate. I will make up a few ml of each, freebase and salts, and see if there is any difference.
At least then, I know I am heading in the right direction.

In terms of alkaloids, the carbolines make up about 3% of tobacco and nic 97%. Anything else is likely too small to be significant. Only if the other is some kind of combustion product could carbolines not be the primary answer.

http://www.biopsychiatry.com/maoi-smoke.htm

My reading is that the PF did seem to be on target though the balance was not right (too weak or too strong; and possibly adding too much water and/or ethanol also); if the correct ratio was used i think it would work well. So I do disagree with you there; only when the correct recipe has been tried can we really know.

Unfortunately I don't have the equipment to help out much experimentally, but I'm supportive of anything you can do to shed extra light on the issue, whether it's practically replicable or pure research.

 

[tceight]

In terms of alkaloids, the carbolines make up about 3% of tobacco and nic 97%. Anything else is likely too small to be significant. Only if the other is some kind of combustion product could carbolines not be the primary answer.

My reading is that the PF did seem to be on target though the balance was not right; if the correct ratio was used i think it would work well.

Unfortunately I don't have the equipment to help out much experimentally, but I'm supportive of anything you can do to shed extra light on the issue, whether it's practically replicable or pure research.

or the synergistic ratios of small amounts together.
like the rats self dosing,
nicotine >90 doses,
acetylaldeyde was what, 200?
together they were 400 doses.
then of course, there are 'other' alkaloids/tryptamines etc with effective doses in the micrograms. (not saying they are in tobacco, just an example of how tiny doses can be, especially with long half life metabolites)
good night all.
~~ oh, there is another reason to find a good simple safe tobacco extraction method, and that is an E-juice ban.
I live in Canada, where health Canada see's fit to ban anything the pharmaceutical companies might have to compete with.
They banned Kava Kava here! Proven safe for thousands of years, one study showed that people with existing liver problems might be affected, and even then, only if the the herb was improperly prepared.
I digress. lol

 

[kinabaloo]

or the synergistic ratios of small amounts together.
like the rats self dosing,
nicotine >90 doses,
acetylaldeyde was what, 200?
together they were 400 doses.
then of course, there are 'other' alkaloids/tryptamines etc with effective doses in the micrograms. (not saying they are in tobacco, just an example of how tiny doses can be, especially with long half life metabolites)
good night all.
~~ oh, there is another reason to find a good simple safe tobacco extraction method, and that is an E-juice ban.
I live in Canada, where health Canada see's fit to ban anything the pharmaceutical companies might have to compete with.
They banned Kava Kava here! Proven safe for thousands of years, one study showed that people with existing liver problems might be affected, and even then, only if the the herb was improperly prepared.
I digress. lol

1/30 is already verging on 'trace amount'.

The acetaldehyde is a MAOI precursor.

BTW, I think carbolines are also banned in Canada.

On big pharma :

http://www.youtube.com/watch?v=UIm8fHxqUAM

 

[HeatherC]

Its actually surprising that the governments haven't tried to ban dihydrogen monoxide yet....

 

[kinabaloo]

Its actually surprising that the governments haven't tried to ban dihydrogen monoxide yet....

Unbelievably almost, the humor has a dark side that is closer than one might imagine.

There are plans to make growing your own food illegal in the US.

And possession of (non-GM 'terminator') seeds.

I wouldnt be surprised if pure / natural water is banned, or tampered, to make sure everyone gets the health destroying fluoride.