Potentation of mescaline/PEA/tryptamine with aldehyde dehydrogenase inhibitors

[Allylbenzene]

Whilst MAO inhibition is a well-known method of potentiation, the use of aldehyde dehydrogenase (ALDH) inhibition is more obscure. Aldehyde dehydrogenase catalyzes the oxidation of aldehydes to carboxylic acids (eg acetaldehyde -> acetic acid).

The main sources of endogenous aldehydes are MAO and SSAO which metabolise amines into aldehydes, eg:

• serotonin into 5-hydroxyindole-3-acetaldehyde
• tryptamine into indole-3-acetaldehyde
• phenethylamine into phenylacetaldehyde
• tyramine into 4-hydroxyphenylacetaldehyde
• dopamine into 3,4-dihydroxyphenylacetaldehyde
• mescaline into 3,4,5-trimethoxyphenylacetaldehyde

- https://doi.org/10.1351/pac200173091393

It's often assumed that MAO is responsible for deaminating mescaline but SSAO seems to play a more prominent role.

The enzyme responsible for the deamination of mescaline to the aldehyde derivative is still a controversial issue among the scientific community. This reaction may be carried out by a monoamine oxidase (MAO) or a diamine oxidase (DAO). Studies with mice have shown that this route is inhibited by TPN, nicotinamide, iproniazid, semicarbazid, and other inhibitor compounds of mono or diamine oxidase [43, 78].
- https://doi.org/10.2174/1874467211666181010154139

Both Iproniazid and semicarbazide are SSAO inhibitors, and Diamine oxidase (DAO) is part of the SSAO family.

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Taking the example of phenethylamine (PEA), MAOB inhibitors are commonly used to potentiate PEA (often using excessive 1g+ doses) but ALDH inhibitors have also been explored. These produced novel results worthy of further investigation. With proper ALDH inhibition the active PEA dose is much more reasonable (200-500mg) and the psychoactive effects are of a completly different nature, longer lasting with a gradual reduction in potency. Usually PEAs effects last for 5 mins to a few hours if there are any effects at all; this is also the case for tryptamine which Shulgin reports little if any effects.

Of course I'm not implying that PEAs aldehyde metabolite is active but that it acts as a prodrug of some sort.

The influence of ALDH inhibition on mescaline has been investigated, albeit a while ago. This is documented in Trouts notes: The Cactus Alkaloids

Inhibition of aldehyde dehydrogenase by calcium carbimide "severely" enhances the pharmacological effects of mescaline in rabbits. Neff & Rossi 1963 cite Friedhoff & Goldstein 1962.
...
In rabbits, which show no symptoms from mescaline, pretreatment with calcium carbimide causes some effect whereas calcium carbimide by itself does not. Since there is no way to know how a rabbit would respond to mescaline if they could respond to mescaline, it is not entirely clear what this means. It certainly is interesting and implies there may be need of follow up research.
...
Rabbits, which are estimated to be about 70 times more tolerant to mescaline than humans, developed "severe" reactions when given very small doses of mescaline after pretreatment with calcium carbimide implying that aldehyde dehydrogenase inhibition enhances the pharmacological activity of mescaline

These are the only reports i've found on the combo of mescaline + ALDH inhibitor.

If mescalines aldehyde metabolite is somehow necessary in it's effects then the ideal potentiation strategy would facilitate it's formation (by SSAO) and minimise it's removal by ALDH. The only inducer of ALDH i've found is sulforaphane (common supplement) which would theoretically weaken mescalines effects. A true SSAO inhibitor would also theoretically weaken mescalines effects.

There are a few suitable food-based ALDH inhibitors:

• starfruit
• diallyl trisulfide from garlic
• diethyl disulfide from durian (ref1, ref2)
• pomegranate
• menthol

To clarify, I do not recommended that ALDH inhibition be used with any potent drugs like 2C-B, MDMA, DMT, psilocybin, amphetamine etc since results might be unpredictable. This ALDHI method is only suitable for less potent drugs like plain phenethylamine, mescaline and possibly tryptamine - but doses should still be kept very low.

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Predosing the ALDHI works best.
Pomegranate juice works best, pre-dose with 500ml then drink some periodically throughout the experience. If using garlic as the ALDH inhibitor look for garlic supplements with the highest allicin content.

ALDH activity was inhibited in the kidney after DATS administration.
...
Diallyl trisulfide (DATS) is one of several compounds produced by hydrolysis of allicin.
Allicin is an organosulfur compound obtained from garlic and leeks. When fresh garlic is chopped or crushed, the enzyme alliinase converts alliin into allicin, which is responsible for the aroma of fresh garlic.

Predosing with the common supplement L-lysine for a day or more (the longer the better) can further amplify things. It helps to minimise choline-rich foods (eg eggs, dairy, meat) since choline contributes significantly towards the production of dimethylamine via gut bacteria transformation.

Here's the technical bit:

If we assume that the whole process of alkaloid production is taking place in the intestines then probably enzymes beyond human enzymatic capabilities might be involved. The process is probably mainly carried out in the jejunum, where the pH is around 8, between 7-9.
...
The transformation process of L-lysine to 1-piperideine is though. It's a natural defense mechanizm of intestinal flora against pathogens, 1-piperideine is toxic to bacteria like salmonella or shigella. I think that the condensation reaction would rather begin with 1-piperideine than the piperidine, because of the double bond, and because it's a natural product of intestinal flora. The enzyme essential to this reaction is primary-amine oxidase, it's a copper containing enzyme like SSAO, it can also be inhibited by semicarbazide. Probably it's inhibited by the same or almost the same compounds which can inhibit SSAO. It's essential because of aldehyde being an intermediate.

• L-lysine -> cadaverine -> 5-aminopentanal -> 1-piperideine
• ^lysine decarboxylase -> primary-amine oxidase -> spontaneous conversion

There is also a corresponding reaction for 1-pyrrolidine

• L-ornithine (or L-arginine) -> putrescine -> 4-aminobutanal -> 1-pyrroline
• ^[Putrescine can be made by various pathways] -> putrescine oxidase -> spontaneous conversion

 

[Allylbenzene]

Here's a report where pomegranate juice significantly potentiated amphetamine. He/she was using pomegranate for its Carbonic anhydrase inhibition effect but wasn't aware that it also inhibits ALDH. Any influence on P450 CYP enzymes is not too important for amphetamine.

 

[red22]

Text in screenshots doesn't show up in the search and isn't easy to read on a phone. If you want to dress up your posts with screenshots, you should include them in addition to the text.

 

[KurtAurelius]

would pomegranate or similar work for Methylphenidate?

I’ve never come across this concept (AD inhibitors) and only having a childlike understanding of MAOs as it is..

 

[Allylbenzene]

would pomegranate or similar work for Methylphenidate?

It wouldn't work for Methylphenidate.
Yes it should work.
Garlic supplements high in allicin and menthol will also work, it's sold in supermarkets as "IBS relief capsules with peppermint oil". It has it's own subtle psychoactive effects, boosting nicotines dopaminergic effect for example.

ALDH inhibitors only seem to work for phenethylamine-type and tryptamine-type drugs. That includes phenethylamine (OTC supplement), mescaline, dopamine, adrenaline, serotonin, tryptamine and amphetamine.

IMO one reason that ALDH inhibitors potentiate amphetamine is because it acts as a norepinephrine/dopamine reuptake inhibitor (NDRI) and monoamine releasing agent. This means it increases dopamine/noradrenaline in two different ways. It's likely that ALDH inhibitors potentiate dopamine/noradrenaline in the exact same way that they potentiate phenethylamine.

Methylphenidate is also an NDRI, like amphetamine.

Fwiw, phenethylamine occurs naturally in cacao nibs so drinking 500ml+ pomegranate juice then eating lots of cacao nibs might be interesting. Cacao nibs are known to have stimulating effects.

 

[red22]

Fwiw, phenethylamine occurs naturally in cacao nibs so drinking 500ml+ pomegranate juice then eating lots of cacao nibs might be interesting.

"And the amount of PEA in chocolate is extremely small; there’s 25 times as much PEA in a wedge of cheddar cheese as in an equivalent amount of chocolate, and even more in smoked salami,"

Chocolate, love and myth-information. Mary Lou Williams, M. Ed. Fort Myers Beach Observer. 2009-2-12.


"Another substance present in chocolate is phenylethylamine, which is also found in low concentrations in the brain. Phenylethylamine releases dopamine and therefore acts in the same way as amphetamines. One might predict that it is this which is ‘addictive’. Studies have demonstrated that 2-3g of phenylethylamine is needed to have anti-depressant properties, but a 50g bar of chocolate contains only a third of a milligram. Moreover, phenylethylamine is broken down readily by monoamine oxidase, so a monoamine oxidase inhibitor would be needed to stop it being broken down in the digestive system."

British Nutrition Foundation conference report: Stimulating thoughts: caffeine and food. BNF Nutrition Bulletin, 23, Winter, 1998, 226-233. (FOOD CRAVINGS AND CHOCOLATE - A PSYCHOLOGICAL OR PHARMACOLOGICAL PHENOMENON? page 231)

Cacao nibs are known to have stimulating effects.

Cacao contains caffeine and a related chem, theobromine.

 

[tryptakid]

I've always been a fan of pomegranate and a lover of cacti and amphetamine. Seems like I should endeavor to do a bit of a Pom-challenge and see if I notice anything different when combining dexamp with pom juice. I also have a fair bit of mescaline tucked away in the safe so that could be a nice way to play with it as well. I'll report back if I have any opportunities to explore this. Thanks for posting @Allylbenzene

 

[red22]

I've always been a fan of pomegranate and a lover of cacti and amphetamine.

Together?

… There's a connection between mescaline and amphetamine.

Alternate name for mescaline: trimethoxyphenethylamine

Alternate name for amphetamine: alpha-methyl-phenethylamine

Also see this post of mine. @Allylbenzene made the next post in that thread, which is basically a prototype of this thread.

 

[Allylbenzene]

I've always been a fan of pomegranate and a lover of cacti and amphetamine. Seems like I should endeavor to do a bit of a Pom-challenge and see if I notice anything different when combining dexamp with pom juice.

Sounds good.
There are many applications for this ALDHI method.

• Phenethylamine (low doses)
• Tryptamine (or tryptophan)
• Mescaline

The essential method is to pre-dose your ALDH inhibitor(s) of choice and optionally pre-dose L-lysine to boost endogenous piperidine. I suggest starting with conservatively low doses of your chosen amine in case the potentiation takes you by surprise.

Interestingly, with plain tryptamine and an ALDHI there's no need to have access to DMT. Choline boosts endogenous dimethylamine levels, lysine boosts endogenous piperidine, and arginine boosts endogenous pyrrolidine.

 

[tryptakid]

Together?

… There's a connection between mescaline and amphetamine.

Alternate name for mescaline: trimethoxyphenethylamine

Alternate name for amphetamine: alpha-methyl-phenethylamine

Also see this post of mine. @Allylbenzene made the next post in that thread, which is basically a prototype of this thread.

Together would be a stretch, though I am rx'd amphetamine so there have been times where I've been technically on mescaline and amphetamine at the same time. Generally I take the lowest possible dose of amphetamine on a day when I am going to trip - especially if I'm using something like mescaline or MDMA given that they're both phenethylamines.

There's a definite connection between them - one of the more interesting psychedelics I've used is 3c-p which in low doses behaves almost exclusively as a traditional amphetamine, however as you increase dose to 20-40mg starts to diverge from a pure stimulant into psychedelic amphetamine land - doses of 70 or 80mg are much much more psychedelic still.

I haven't played around with DOB or DOC though I do have some and may try them at some point. I've always been cautious as I've developed some pre-hypertension over the past few years and haven't wanted to put myself at risk of hypertension while tripping. I've recently gotten my BP back down to normal levels consistently so I may consider revisiting some of these drugs at some point. I've taken mescaline during this period but didn't want to risk trying something entirely novel and known for having a large cardio load in the way that the DOB/DOC reports seem to indicate they do.

I've always gravitated towards pomegranate as a flavor and I do wonder if there's something about it beyond just taste that I find compelling.

 

[unodelacosa]

with plain tryptamine and an ALDHI there's no need to have access to DMT.

What if someone wanted to smoke some DMT? Somehow I find it hard to believe that if I predose with an ALDHI I can simply smoke tryptamine and it will have the same effect as smoking DMT…

 

[Allylbenzene]

What if someone wanted to smoke some DMT? Somehow I find it hard to believe that if I predose with an ALDHI I can simply smoke tryptamine and it will have the same effect as smoking DMT…

I can't comment on the smoking ROA since all tests were done using oral ROA. The MAO enzyme makes the aldehyde which finds either dimethylamine, piperidine or pyrrolidine.

The most common is dimethylamine since most people choose choline-rich foods. When someone takes a lysine supplement, gut bacteria eventually convert the lysine into piperidine thus boosting endogenous levels of piperidine. When someone takes an arginine supplement the same occurs producing pyrrolidine.

Since everyone has different levels of gut bacteria conversion times will vary. Predosing the choline, lysine or arginine for several days will ensure stable levels.

In some ways this ALDHI method has advantages over regular DMT since tryptamine is very easy to acquire and choline is a standard supplement. I do not recommended trying it with amphetamine-type drugs, 2C-X drugs or substituted tryptamines.

 

[4DQSAR]

Antabuse (disulfuram) is an example of an ALDH inhibitor. I've read some clinicians also use Cyanamide (calcium carbimide) to treat the same condition i.e. dipsomania.

Or if one seeks a natural product, tippler's bane mushrooms contain compounds with similar activity.

I believe several antibiotics also have such activity and a few other medicines.

I in no way wish to infer that the non-prescribed consumption of any of these things is a good idea.