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This might give you some idea.

 

For an extract that exerts beneficial CNS effects:


Catha edulis Forsk. (Khat): Evaluation of its Antidepressant-like Activity

Although a lot of studies demonstrated that cathinone is unstable and undergoes degradation during drying or extraction and becomes physiologically inactive after about 36 h of harvesting,[8,22,23] the current investigation used standardized extraction method followed by spectroscopic confirmation. The phytochemical analysis (MS of Khat extract) indicated the presence of cathinone and cathine as shown in Figure 1.

 

Previously published studies on the chemical compositions of herbs and their bioactivity recommend that plants containing saponins, flavonoids, and tannins own bioactivity against many central nervous system ailments.[31] Phytochemical data on Khat revealed the presence of many phytochemicals.[32] It is probable that the biomechanism of anxiolytic action of Khat could be due to the binding of cathine or cathinone to various receptors involved in the anxiolysis processes, which has to be explored further.

Wont go into isolation of active constituents here.

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Thanks mate! Whoa, that's some seriously sexy recently published data. Imma have me a closer look at it on the weekend.

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On 3/7/2018 at 11:45 PM, Martyh64 said:

Does anyone know what the rough percentage of Cathine + Norephedrine would be in an extract of dried (oxidized) Catha Edulis leaves? read that cathinone also breaks down into other chemicals after picked, would like to know what the ratio is and if there would be any way to separate them from the Cathine.... For science :) theory only of course!

Fresh khat might contain around 1% (wrong - see correction below) cathinone by weight (it's hard to get accurate numbers as many extraction methods hasten the breakdown). If dried poorly, nearly all of that can be converted to other compounds like cathine - stored at room temp one study ( Degradation of cathinone from Catha edulis (khat) leaves ) observed that 50% of the cathinone was lost by the 2nd day, and almost all of it was gone by day 3. But if you can prevent these reactions, then the cathinone stays cathinone (it's stable once extracted, or well-dried), and you don't need to worry about separating out the breakdown products, as they just won't be there!

 

The trick to preserving the cathinone seems to be to dry the leaves as quickly as possible, or freeze them:

Quote

Evaluation of the effect of various drying techniques on the composition of the psychoactive phenylpropylamino alkaloids of khat (Catha edulis Forsk) chewing leaves

M. Atlabachew, B.S. Chandravanshi, M. Redi-Abshiro, N. Torto, S. Chigome, B.O. Pule

Abstract

The study demonstrated that by freezing or drying under different conditions, cathinone could be detected in the khat (Catha edulis Forsk) samples that have been harvested for more than four months. Freeze drying or freezing in the refrigerator (-20 oC) yielded more than 73% of cathinone. Air drying, sun drying or oven drying at 60 oC resulted in a cathinone composition of 57%, 42% and 36%, respectively. The study confirmed that, freshly harvested tender leaves of khat contained exclusively of cathinone but upon sun drying, part of it decomposes to cathine and norephedrine leaving cathinone as a major component. Thus it is wrong to assume that sun drying the leaves can result complete conversion of cathinone to cathine and norephedrine. Furthermore, the results of the study confirmed that it was possible to preserve khat samples for longer periods after freeze drying or deep freezing without significant loss of cathinone.

 

Using a little heat (sun or oven) to speed up the drying process might not be ideal, but is probably better than leaving half-dried leaves sitting around (eg. in a humid climate where they won't dry in a day) - keeping a third of the cathinone is still better than losing all of it.

Edited by Anodyne
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4 hours ago, Anodyne said:

Fresh khat might contain around 1% cathinone by weight (it's hard to get accurate numbers as many extraction methods hasten the breakdown). If dried poorly, nearly all of that can be converted to other compounds like cathine - stored at room temp one study ( Degradation of cathinone from Catha edulis (khat) leaves ) observed that 50% of the cathinone was lost by the 2nd day, and almost all of it was gone by day 3. But if you can prevent these reactions, then the cathinone stays cathinone (it's stable once extracted, or well-dried), and you don't need to worry about separating out the breakdown products, as they just won't be there!

 

The trick to preserving the cathinone seems to be to dry the leaves as quickly as possible, or freeze them:

 

Using a little heat (sun or oven) to speed up the drying process might not be ideal, but is probably better than leaving half-dried leaves sitting around (eg. in a humid climate where they won't dry in a day) - keeping a third of the cathinone is still better than losing all of it.

Thanks for sharing Anodyne, this is exactly what I was looking for :) 

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About the study Alchemica linked to (this one) suggesting "anti-depressant-like" effects, there are some real problems with their study design that you should consider before accepting their conclusions, especially these bits:

 

Quote

The current results suggest that the extract of Khat leaves has acute antidepressant properties and may have sedative effects...

 

...It is probable that the biomechanism of anxiolytic action of Khat could be due to the binding of cathine or cathinone to various receptors involved in the anxiolysis processes, which has to be explored further. The results found in this study propose that the extract of the leaves of Khat possesses anxiolytic and muscle relaxant activities.

 

In the first part, they seem to actually mean "anxiolytic" and just using "sedative" as a synonym, which it isn't. I can't even work out where the "muscle-relaxant" claim is coming from at all - unless it's mentioned in one of the other papers they reference - they seem to just be pulling that out of their arse. That they didn't make a quantitative analysis of their extract is also an issue, as it makes duplication difficult - they confirmed that cathinone was present, but we have no idea how much.

 

But the major issue is the tests they've used to screen for "anti-depressant-like" activity, and their limitations: the forced-swim-test (FST), tail-suspension-test (TST) & hole-board-test (HBT). In the first two, the rodents are deliberately put into an uncomfortable/stressful situation, then the researchers time how long they keep struggling or trying to escape. The test ends when they stop moving, and that time is recorded. It is assumed that they stop moving because they've given up & lost hope of escaping. Leaving aside the problems of acute-vs-chronic-depression-models (which this article covers well: Doubt about antidepressant-like effect ), a big issue when using these tests for any kind of stimulant drug is that the rodents might keep moving around longer just because of the stimulant effects, and not because of any anti-depressant actions.

 

This isn't to say these tests have no value, just that in the particular case of investigating stimulants (or depressants), they should be paired with other tests which take that into account, and try to separate the drugs effects on locomotor activity from its effects on mood. Given that this limitation was mentioned in the very first discussion of the TST in 1985, the fact that it's completely ignored in this 2017 paper (not only in their study design, which could be due to time/cost limitations, but also in their discussion/conclusion) is pretty inexcusable.

Quote

"Antidepressant drugs decrease the duration of immobility, as do psychostimulants and atropine. If coupled with measurement of locomotor activity in different conditions, the test can separate the locomotor stimulant doses from antidepressant doses."

 

The tail suspension test: a new method for screening antidepressants in mice

 

Here's a few more recent papers which also discuss this problem & suggest some possible ways to account for it:

 

Tail suspension test does not detect antidepressant-like properties of atypical antipsychotics

Anti-immobility activity of different antidepressant drugs using the tail suspension test in normal or reserpinized mice - "Comparison of anti-immobility activities of putative anti-depressants in non-pre-treated and in reserpine-pre-treated mice, using the tail suspension test, may be useful to discriminate amphetamines from antidepressant drugs and to differentiate between categories of amine re-uptake blockers"

Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety - "These results confirm that under certain test conditions, psychostimulants are capable of producing "false-positives" in elevated maze models, and that both traditional methods and the ethological measures used in this study fail to unequivocally dissociate drug effects on anxiety from effects on locomotor activity." (different test, but maybe applicable)

 

And the other test used (which measures how much the animals will explore an unfamiliar environment, and assumes a link between this behaviour & anxiety levels) has similar limitations:

 

Some doubts about the basic concept of hole-board test  - "It is concluded, that the inverse relation between anxiety state and head-dipping activity is true only in a certain range of anxiety level. In more aversive situations, when the anxiety level of the animals is high, the holes nay represent a possible way to escape from the aversive environment instead of an explorable object."

The exploratory behaviour of rats in the hole-board apparatus: Is head-dipping a valid measure of neophilia? - "Many unconditioned tests, such as the open field, potentially confound general locomotor activity with exploration. The hole-board apparatus appears to avoid this confound, as head-dipping into holes in the floor is assumed to be a valid measure of the subject's attraction towards novelty (neophilia).... Rather than being a measure of neophilia, these results support the hypothesis that head-dipping represents an escape response, which declines as the subject becomes less fearful."

 

Summary version is that it seems more likely to me that the behaviour observed in that 2017 study could be attributed to khat's stimulant effects, rather than any anxiolytic/anti-depressant action.

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I wonder if doing a vodka extraction in the freezer would be effective at getting cathinone into a stable solution without it degrading? That will have to wait until my bushes are bigger before I know. Maybe someone else could try.

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Stable in acidic EtOH solution from memory. Freeze drying would be preferable I'd guess. 

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Damn, vodka-khittie-sours sounds like a dangerous mix. Freeze-dried leaves may be more stable/high-yielding/whatever, but also contain significantly less delicious counteractive drug combo.

 

I wonder if my plants are big enough to massacre for an experiment? Any reports, people?

 

(also someone please bring back OTC codeine so catha-booze stops sounding like a good idea. Pre-mixed drinks are never a good idea.)

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1 hour ago, Anodyne said:

(also someone please bring back OTC codeine so catha-booze stops sounding like a good idea. Pre-mixed drinks are never a good idea.)

Desperate times call for desperate measures...

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No codeine sux ass! I personally think all opiates suck unless u r in pain. Recreationally I wouldn't go near opiates. Except maybe the occasional O pipe. Kh at is strange. Some days the plant is weak, some days it is strong. Changes daily too. Early morning seems best. U can tell by the taste. Bitter one day, mild the next. Massive wads uncomfortably crammed in the cheeks. Wash down bitter juice with red bull or other cafinated beverage for synergy. U get to a strange state, sumwhat stimulated, but fucked out like alcohol or md gurn. It's definitely not conducive to getting stuff done around the house. Each variety is different. These descriptions are of the PH variety which has narrow leaf genes mixed with red genes. Red alone or narrow alone may be subjectively different. I'd be interested if someone could isolate the (presumably cathedulin) that is responsible for the more inebriating effect. It may be worthy of medical investigation for certain situations. 

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On 3/18/2018 at 0:10 AM, Anodyne said:

Fresh khat might contain around 1% cathinone by weight

Correction - that should have said "0.1%" - so 100g fresh leaves yields around 100mg* cathinone. Some researchers have gotten ~1% yields from dried material. Sorry about that!

 

(*anywhere between 30-300mg seems pretty standard - though the lower yields tend to have much higher ratios of cathine+norephedrine, suggesting that their cathinone yields could've been higher with less destructive storage/extraction methods.)

 

I also shoulda mentioned that the cathinone->cathine conversion isn't limited only to harvested leaves - the older leaves on the plant will also contain cathine (ref). Again the data is sketchy & results vary depending how they went about it, but lets say 50:50 with cathinone. So even though older leaves aren't as good to chew (not just because of the lower cathinone levels, but also because they're full of saponins, tannins, & tough fibres), they work just fine for making tea, as the cathine is heat-stable. The effects (less euphoric, more straight-up stimulant) may not be as nice as chewing high-cathinone fresh material, but it's one way to make use of old leaves.

 

Kind of a middle-ground between tea (cathinone-destroying) & chewing quids (which is not really socially-accepted in Oz as a drug ROA) might be this method where they just chuck fresh leaves & cold water (1g/ml) into a high-speed blender, strain thru a cloth, and then freeze the "juice" until needed. They were only storing it for a short time, but it'd be interesting to see how the cathinone held up in frozen juice prepared this way. I'm guessing you'd actually be speeding up the degradation reactions (as all those enzymes would end up in your extract, plus extra oxygen+light, less protective cell walls...) if you left the juice sitting around at room/fridge temp, and probably even at freezer temps some breakdown would continue... but it might be ok for an immediate-use situation, especially if quid-chewing wasn't your thing?

 

As a side note, "khatamines" (I guess coined by these researchers) is a great term & should be used more often.

Edited by Anodyne
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22 hours ago, Martyh64 said:

So if one wanted to guarantee total or near total breakdown of all the cathinone in leaf into cathine and noreph you could just boil the leaves?

If you were going for quick/easy/food-safe with min ingredients, then.. maybe? Some folks have suggested that boiling might actually denature the enzymes which are mostly responsible for that conversion though - I'm not sure if there was any research to back that up, but if your goal was maximum breakdown, then it might be best to let the leaves sit in a bag (in the fridge?) for a few days or something before boiling, just to give those enzymes extra time to work their mischief?

 

I seem to recall researchers running simple reduction reactions to give the results you describe, but that would've been using isolated cathinone - I'm guessing that trying to do the same thing on a crude extract would likely get messy fast & cause a whole heap of unintended reactions & byproducts.

Edited by Anodyne
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I made some calculations based on the Cathine / Cathinone content and also searched the literature for dosages of leaves, which were hard to find.

I came to the conclusion that you need 100 - 200 g fresh Kath- leaves for one dose.

Dried leaves have a 3,3 times lower weight than fresh leaves.

Calculating with the effective Cathinone- dose for 60 kg body weight whould be 310 g fresh leaves for an action which is comparable with Amphetamine.

To factor also the Cathine content into the calculation (which only has a tenth of the efficacy of Cathinone), it has a 3-times higher content in the fresh leaves, in dried leaves the Cathine- content is even higher because of the conversion on Cathinone to Cathine during the drying process. Because 100 g Kath leaves contain 83 - 120 mg Cathine and an active dose of Cathine is 16 - 53 mg.

So it can be concluded that: although there can be felt minimal effects from 10-15g Kath leaves, for medium strength effects there must be consumed at least 50 - 100 g leaves.

 

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The Cathinone and Cathine have very uneven distribution in the plant:

 

Catha edulis- Wirkstoffanteile der verschiedenen Pflanzentei.jpg

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Potency of Cathinone and Cathine vs. Ephedrine and Amphetamine:

This can be explained by the different affinity for Dopamine-, Norepinephrine- and Serotonin- releasing:

 

Cathin, Cathinon u.a. Monoamin Releasing Agents (MRAs).jpg

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