Is there way to find out if I still have Harmalas in my system?

[steppa]

Hey Nexus,

this bothers me. I really want to know how long smoked harmine freebase is active in my system.

I've done some reading on the interwebz and am more confused than ever now, cause there are so many contrary statements.

I found all kinds of contrary statements on the web as well as here on the nexus, reaching from "smoked harmine is active for about an hour" to "smoked harmine is active for about 24 hours".

This bothers me.

Wikipedia says:

Harmine half life: The plasma elimination half-life is on the order of 1–3 hours.

and states "R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 727-728." as source.

Now I'm aware that different people have different metabolisms. And that it is, due to this fact, nearly impossible to give a universal timescale.

What I am asking for is the following:

Is the anything that can indicate if one still has active harmalas in ones system?

My wild running imagination imagines somthing like an indicator substance which one could consume and which has a certain recognizable effect of some kind. Is there anything like that? Or any other way to find out more about ones personal harmine metabolism? ...except eating DMT.

 

[Ufostrahlen]

Could give you some hints:

Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics

Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics

The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically...

jpet.aspetjournals.org

Urine Samples. Urine was collected in fractions of 0 to 8 h, 8 to 16 h, and 16 to 24 h in plastic containers with 3 ml of 6 N HCl and kept in the refrigerator during the 0- to 24-h collection period. Volunteers took home the two plastic containers corresponding to the 8- to 16-h and 16- to 24-h periods. Volume of each fraction was recorded and pH was adjusted to 2 to 4 with 6 N HCl, and two 50-ml aliquots were frozen at –20°C and stored at –80°C until analysis. The following monoamine metabolites, VMA, HVA, 5-HIAA, metanephrine, and normetanephrine were quantified by means of HPLC with coulometric detection following previously validated procedures (Soldin and Hill, 1980; Parker et al., 1986; Gamache et al., 1993). The limit of quantification was 3 mg/l for VMA, HVA, and 5-HIAA, 0.05 mg/l for metanephrine, and 0.10 mg/l for normetanephrine.

Harmol glucuronide and harmol sulfate have been described as the main urine metabolites of harmine following its i.v. administration in humans (Slotkin et al., 1970).

They also have plasma half-life curves for various compounds, e.g.:

http://jpet.aspetjournals.org/content/306/1/73/F4.large.jpg

Related reads for harmala pharmacokinetics:

Pharmacokinetics of Hoasca alkaloids in healthy humans
http://fii.fi.tartu.ee/~helle/kool/AYA/Aya/Callaway1999.pdf

Quantitation of N,N-Dimethyltryptamine and Harmala Alkaloids in Human Plasma after Oral Dosing with Ayahuasca

Quantitation of N,N-Dimethyltryptamine and Harmala Alkaloids in Human Plasma after Oral Dosing with Ayahuasca

Abstract. Harmine, harmaline, tetrahydroharmine (THH), and N,N-dimethyltryptamine (DMT) were quantitated in plasma from 15 healthy male volunteers after the ing

jat.oxfordjournals.org

 

[steppa]

Wow Ufostrahlen, thank you! This is relevant to my interests.

All those charts and studies refer to oral consumption of harmine.

But I assume that those charts would look significantly different, if the harmine was smoked/vaped, instead of being consumed orally. Is this correct?

 

[Ufostrahlen]

I guess the onset would be much faster, yet the enzymatic breakdown should be the same. I.e. the decline after the peak should look identical.

 

[steppa]

Again...

...thank you very much!

 

[Ufostrahlen]

You're welcome. Something I'd like to add: Pharmacokinetics are also dose-dependent. So if you want similar looking curves for smoked harmalas, compare it with similar oral doses. Also the absorption for smoked vs. oral harmalas may vary.

Bioavailability - Wikipedia

en.wikipedia.org

First pass effect - Wikipedia

en.wikipedia.org

Alternative routes of administration like suppository, intravenous, intramuscular, inhalational aerosol, transdermal and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation. Note that the intravenous route also avoids the absorption phase.

But once you got the harmalas in your system, the metabolic pathway should be the same.

 

[steppa]

Pharmacokinetics are also dose-dependent. So the if you want similar looking curves for smoked harmalas, compare it with similar oral doses.

It's great how you are able to understand my stupidity on this topic and to point out what's relevant for me.

Maybe I'm allowed to stress your patience once again.

Ok. The total amount of harmine by percentage, which really gets into the system is higher when smoked/vaped because it avoids the first pass effect.

Now...this chart...

The box said that 204mg harmine were consumed. Those 204mg produced a peak level at a certain mark.

Can one assume that the graph for harmine can be scaled proportionally to the dose consumed?

The red line would then be my asumption for 30 mg of smoked harmine.

I basically copied the curve and scaled it down to a peak to a level I just _guessed_. Also I made the onset a bit steeper.

Would you say that this way of thinking could be correct. Or would you say this is plain wrong?

 

[Ufostrahlen]

Can one assume that the graph for harmine can be scaled proportionally to the dose consumed?

Well, I was speaking in general terms, now that's a very specific question. It seems logical to me, but maybe there are factors I'm not aware of. I'm not a studied pharmacologist. Maybe we have someone on the Nexus with this expertise who can comment?

Would you say that this way of thinking could be correct. Or would you say this is plain wrong?

I wouldn't say it's plain wrong. My understanding is that the shape of your curve looks good, but in the end I wouldn't bet money on it. The curve could also peak at 40ng/ml, because the lung may absorb harmalas much better. But then there are factors which I don't know. Do some harmalas get burned? How deep do you inhale and how long do you have to hold the breath for max. absorption?

Too much uncertainty to give precise statements.

 

[steppa]

I wouldn't say it's plain wrong. My understanding is that the shape of your curve looks good, but in the end I wouldn't bet money on it. The curve could also peak at 40ng/ml, because the lung may absorb harmalas much better.

Yes. I understand this. Thank you.

Ok. I see. For me...to become certain...I might have to bite the bullet and swallow some dmt after a certain ammount of time and see if something happens.

 

[universecannon]

Are you worried about drug interactions, a drug test, or just curious? I once went into a drug test for work once while still on harmalas from the night before without issue. As far as I know, no one tests for them.

 

[steppa]

Are you worried about drug interactions, a drug test, or just curious?

Hehe. It's a combination of the first and the third.

 

[steppa]

Just to condense my actual questions into one sentence each...

Question 1:

My wild running imagination imagines somthing like an indicator substance which one could consume and which has a certain recognizable effect of some kind. Is there anything like that?

Question 2:

Can one assume that the graph for harmine can be scaled proportionally to the dose consumed?

 

[DreaMTripper]

I wouldn't say it's plain wrong. My understanding is that the shape of your curve looks good, but in the end I wouldn't bet money on it. The curve could also peak at 40ng/ml, because the lung may absorb harmalas much better.

Yes. I understand this. Thank you.

Ok. I see. For me...to become certain...I might have to bite the bullet and swallow some dmt after a certain ammount of time and see if something happens.

This wouldnt work im afraid as the mao in your stomach is unaffected (or barely affected) when you smoke it.

 

[steppa]

This wouldnt work im afraid as the mao in your stomach is unaffected (or barely affected) when you smoke it.

Arrrgggh.

Thank you. I speculated about this yesterday in my head and now I'm sure too that this woudn't work.

So I'm in a little dilemma here. How to get out of it?

 

[steppa]

Hey Nexus,

another thing regarding harmine...

I found this Study:

Effect of monoamine oxidase inhibition on amphetamine-evoked changes in dopamine receptor availability in the living pig: a dual tracer PET study with [11C]harmine and [11C]raclopride.

It says:

Abstract
The activity of both isozymes of monoamine oxidase (MAO) is reduced by 50% in the brain of human smokers. We hypothesized that this is not an epiphenomenon, but should bring about potentiation of the action of psychostimulant drugs. To test this hypothesis, we carried out serial positron emission tomography (PET) studies in Göttingen miniature pigs to measure the binding of the MAO-A ligand [11C]harmine and to measure the changes in [11C]raclopride binding evoked by a low dose of amphetamine (0.7 mg/kg as free base, i.v.), first in a baseline condition, and, one month later, after acute treatment with pargyline (2 x 3 mg/kg as free base, i.m.). In the baseline, the distribution volume of [11C]harmine relative to the arterial input (V(d), ml g(-1)) ranged from 74 ml g(-1) in cerebellum to 139 ml g(-1) in the medial hypothalamus. Pargyline treatment reduced the magnitude of V(d) globally to 34-54 ml g(-1). Nearly complete displacement of [11C]harmine binding was detected in neocortex and striatum, but there was evidence for pargyline-resistant binding in the pituitary gland and diencephalon. In the baseline condition, the low dose of amphetamine evoked a 14% decline in the binding potential (BP) (pB) of [11C]raclopride in striatum (P = 0.026). After pargyline treatment, the amphetamine effect was of similar magnitude (-11%), although not statistically significant (P = 0.054). However, the second amphetamine challenge evoked a 24% reduction in [11C]raclopride pB relative to the original baseline condition (P = 0.018). Present results do not strongly support our hypothesis that MAO inhibition should potentiate the amphetamine-evoked dopamine release as measured in the [11C]raclopride competition paradigm.

...the thing is that this isn't really understandable for a layman. Would someone please be kind enough, to explain this paragraph to me?

I basically understand what they did. But I don't really understand what they found out.

btw. there is originally no smiley in the quote. ...the nexus does this to it.

 

[DreaMTripper]

hahah love the smileys that randomly pop up
The experiment is foreign to me too but the last sentence explains the outcome. Basically, amphetamine releases dopamine
in the brain/ changes dopamine receptor activity, can cause all sorts of problems after long term and short term use, anmphetamine psychosis among many others. They hypothesised that MAO inhibition would increase/ modulate activity at the dopamine receptors significantly, therefore proving MAOI potentiate psychostimulants, the amphetamines, but their findings dont back this up.
Not too sure what field they are in possibly clinical psychiatry but one things for sure there are some majorly tweaked out pigs somewhere!

 

[steppa]

Thank you for the explanation, DreaMTripper. :thumb_up:

 

[pinkoyd]

Regarding your Question #1 steppa it seems to me that somewhere around here there is a thread about someone shining UV light on their pee.

Harmalas flouresce under UV.

Harmalas get excreted by the kidneys.

Therefore urine flouresces when harmalas are in it.

I could be totally wrong on this so do your homework first, but I think it could give you an idea of how long harmalas stay in your system. At least for orally ingested material; smoking might provide too light of a dose to show up.

 

[steppa]

Wow pinkoyd!

Sounds like this idea is worth a try.

Thank you!

 

[steppa]

Hm... I found this BLOOD LEVELS AND URINARY EXCRETION OF HARMINE AND ITS METABOLITES IN MAN AND RATS

I'm not sure if this method would tell me if the mao is still partitionally inhibited, but I guess not.

This study quantifies blood and urinary levels of harmine and its urinary metabolites (harmol, harmol glucuronide and harmol sulfate) in man and rats after the i. v. administration of 0.5 mg of harmine per kg (man and rats) and 5 mg of harmine per kg (rats). Metabolites were analyzed by paper chromatography, enzymatic hydrolysis and fluorometry. Within two minutes after administration, 10% of the dose was found in the blood of either species; after four hours, ≤1%. Both species excreted the same urinary metabolites. After 48 hours, total urinary excretion was about the same, although the excretion rate was higher in man. Urinary harmine and harmol concentrations were insignificant. Harmol sulfate was the primary conjugate in rats; harmol glucuronide excretion predominated in man. The ratio of the rate of harmol glucuronide excretion to the rate of harinol sulfate excretion (G/S) increased with time in rats given 5 mg of harmine per kg, but was relatively constant in rats and humans given 0.5 mg of harmine per kg. Administration of Na2SO3 to rats given 5 mg of harmine per kg prevented this rise in G/S, suggesting that 3'-phosphoadenosine 5'-phosphosulfate plays a limiting role in the formation of harmol sulfate.