Phenethylamines A full guide for ultimate Mescaline potentiation

[Allylbenzene]

The intention behind this technique is to maximise the efficiency of mescaline's activity. No MAOIs or SSAOIs are used since MAO and SSAO must remain active. These enzymes produce the initial aldehyde metabolite which must be protected using an aldehyde dehydrogenase (ALDH) inhibitor. This aldehyde metabolite is inactive but appears to participate in the creation of active metabolites. This guide summarises how to facilitate this process.

The major aspects of the metabolism of mescaline... Of these, oxidative deamination to 3,4,5-trimethoxyphenylacetaldehyde seems to be the most important process, leading subsequently to the acid (TMPAA).
- https://doi.org/10.1021/acschemneuro.8b00215

The advantages include reduced dose requirements, faster onset and a richer experience. With smaller doses comes a reduced risk of nausea. This technique also allows for extended potentiation meaning a single dose can be theoretically perpetuated (recycled) for several days if desired. This "cycling" tek is most suited for specialised purposes. There are several easy options to stop the potentiation effect also.

2 reports on the combo of mescaline + ALDH inhibitor:
- https://i.ibb.co/qL2Gsfsb/image.png
- https://i.ibb.co/N6cLHFmY/image.png

The only requirements are as follows:

• pomegranate juice (1+ litre, ALDH inhibitor) - double check that your pomegranate juice is actually 100% pomegranate.
• pomegranate extract (2nd best choice, standardised for gallic acid)
• lysine supplement (an essential amino acid with an RDA of 37mg/kg/day for adults, turned into piperidine by gut bacteria)
• Optional: sulforaphane supplement (this increases ALDH)

For maximum potentiation, minimise the following items for as long as possible before - and on - the special day:

• choline-rich foods (eg eggs, spinach, wheat, fish, shrimp, meat, dairy, soy)
• cruciferous vegetables (eg broccoli, broccoli sprouts)
• supplements containing taurine, lipoic acid, sulforaphane, vitamin B5 (pantethine), vitamin B6 (pyridoxine), N-acetylcysteine (NAC), garlic, resveratrol, turmeric/curcumin, glucosamine, choline, carnosine, arginine, ornithine, dihydromyricetin
• vegetable (seed, nut) oils and omega 3/fish oils
• pears, cucumbers, tomatoes, garlic, sweet lime & asparagus
• coconut water, black tea, green tea

These items will also make regular mescaline experiences weaker which can be misinterpreted as having a high tolerance. If someone was regularly using large amounts of all the items mentioned above then 800mg of mescaline could be mild or possibly inactive.

Contraindications:

• Avoid drinking alcoholic beverages for 24 hours before, during and 24 hours after the experience since alcohol should not be combined with ALDHIs.
• Avoid all prescription/otc medications for 28+ days before and after the experience.
• Avoid using MDMA, cocaine, amphetamines, 2C-X, St John's wort, Kanna, Ashwagandha, RCs and commercial cigarettes for 7 days before, during and 7 days after the experience.
• Avoid fermented foods and drinks for 24 hours before, during and 24 hours after the experience as these contain small quantities of alcohol and several aldehydes (eg kefir, kombucha, kimchi, sauerkraut, saké, sourdough, yogurt, cheese, sour cream, miso, natto, soy sauce, tempeh).
• Avoid all vegetable (seed, nut) oils and omega 3/fish oil supplements for 28+ days before and after the experience as these either contain toxic aldehydes or form toxic aldehydes after ingestion (eg acrolein, +others). If you have been regularly taking omega 3/fish oil supplements then it's advisable to allow all toxic aldehydes to be detoxified before using an ALDHI for this tek. (To facilitate this process the items mentioned in the previous section will speed up the removal of aldehydes eg cruciferous vegetables, sulforaphane, taurine, NAC etc)

Considerations:

• Start with 1/4 to 1/3 of your usual mescaline dose to assess the degree of potentiation.
• It might be useful to have a sulforaphane supplement on hand as a way to "stop" the potentiation effects if necessary (sulforaphane increases ALDH).
• Other items with similar "stopping" effects include pear, cucumber, tomato, coconut water, black/green tea (potency: 91%, 87%, 41%, 14%, 5%, 3%) and asparagus.
• Items which are synergistic with pomegranate juice: durian, menthol
• I'm aware that pomegranate juice can be expensive but since it's the ideal ALDHI i'd suggest using at least 500ml combined with more affordable pomegranate extract supplements (standardised for gallic acid). If you have menthol sweets or peppermint oil capsules the menthol will contribute. Peppermint oil capsules are commonly sold in supermarkets as a digestive relief aid and have additional anti-nausea benefits.
• The maximum generally safe dose of lysine is 3g/day split into three 1g doses. After taking a lysine supplement gut bacteria eventually convert it into piperidine which boosts endogenous levels. Everyone has different levels of gut bacteria so conversion times will vary. Predosing the lysine for several days will help ensure increased piperidine levels.

The potentiation steps are as follows:

• Predose 500mg–1g lysine daily (max 2g) for as long as possible before the special day, ideally 7+ days. Lysine-rich foods are a valid option but lysine capsules are reliable.
• On the special day keep breakfast/lunch light (no meat, dairy, egg, fish) to minimise nausea and maximise potentiation. Avoid coffee for now, wait till T+120mins to make the most of it's synergistic effect.
• 1 hour+ after last meal, calmly drink 500ml pomegranate juice (PJ) in no particular rush.
• T+00min: Take your mescaline
• T+30min: calmly drink 250ml+ PJ (or capsules)
• T+90min: calmly drink 250ml+ PJ (or capsules)
• Optionally, drink ~150-200ml+ PJ every ~30-60mins to perpetuate (cycle) the experience.
• For extended cycling sessions ensure a healthy supply of electrolytes (Na, K, Ca, Mg) and sunlight if possible. The PJ will supply some electrolytes & natural sugars to fuel oxidative metabolism. Other sources of natural sugars can be explored such as dates. Coconut water seems ideal but will slightly counteract the PJ so isn't recommended. Pears will also counteract the PJ albeit more potently.
• Potential synergistic fruits with ALDHI activity which could be explored alongside PJ: apple, mango, watermelon, papaya (potency: 76%, 62%, 57%, 50%).
• To stop the potentiation use a reasonably large dose of a sulforaphane supplement. Alternatively use broccoli sprouts which contain the highest concentration of glucoraphanin which is a precursor to sulforaphane. Glucoraphanin is water soluble so chewing broccoli sprouts should have a quicker "stopping effect" than sulforaphane.

I'll be updating this as I uncover new info.

 

[4DQSAR]

Or one of the many medicines with established aldehyde dehydrogenase activity?

I can't help but think that MORE mescaline will result in higher plasma levels OF mescaline in a dose-dependent manner.

 

[doubledog]

Fascinating stuff but my experience is that black tea potentiates mescaline due to its caffeine content. Caffeine itself is the best potentiator of mescaline I know of.

 

[Allylbenzene]

Or one of the many medicines with established aldehyde dehydrogenase activity?

These can cause acute mescaline potentiation which can be overwhelming as reported here. I wrote this guide with harm reduction in mind.

Fascinating stuff but my experience is that black tea potentiates mescaline due to its caffeine content. Caffeine itself is the best potentiator of mescaline I know of.

Caffeine is a great potentiator, I mention it in the 2nd potentiation step:

Avoid coffee for now, wait till T+120mins to make the most of it's synergistic effect.

The use of an ALDHI is ideal because it facilities a process which happens naturally, albeit slowly and not as efficiently. Caffeine is likely synergistic because it's a metabolic enhancer which increases the body's metabolic rate (eg mitochondrial function) and has a pro-dopamine effect.

 

[Allylbenzene]

Some insights about mescalines metabolism and it's metabolites:

Although its effects are attributed mainly to its action as a 5-HT2A receptor agonist, mescaline binds in a similar concentration range to 5-HT1A and α2A adrenergic receptors. It is largely excreted unchanged in human urine, and its metabolic products are apparently unrelated to its psychedelic properties. It's low potency is...

Mescaline is eliminated almost completely from the human body within 48h, mostly unchanged ... The major aspects of the metabolism of mescaline...in several mammalian species, including humans. Of these, oxidative deamination to 3,4,5-trimethoxyphenylacetaldehyde seems to be the most important process, leading subsequently to the acid (TMPAA) and the alcohol.

Investigation into the human pharmacokinetics and metabolism of mescaline seems to have come to a standstill after 1978. A question that was occasionally raised up to that time was if the pharmacology of mescaline might be due to one or more of its metabolites.

Source: https://doi.org/10.1021/acschemneuro.8b00215

 

[doubledog]

Caffeine is likely synergistic because it's a metabolic enhancer which increases the metabolic rate (eg mitochondrial function) and has a pro-dopamine effect.

Yeah, that is true, caffeine seems to increase (speed up) metabolic rate of mescaline.

btw. in the link provided it's mentioned that things like apple juice or nutmeg have stronger effects on ALDH. Why not use it instead of pomegranate? Or am I reading it wrong?

 

[Allylbenzene]

...caffeine seems to increase (speed up) metabolic rate of mescaline.

That might be true yes, but I'd clarify that caffeine acts as a metabolic stimulant meaning it enhances the body's metabolic (thyroid) function. This is unlike other stimulants which mainly work via noradrenaline and dopamine (amphetamines, cocaine, methylphenidate etc).

btw. in the link provided it's mentioned that things like apple juice or nutmeg have stronger effects on ALDH. Why not use it instead of pomegranate? Or am I reading it wrong?

Yes, I mentioned apples.

Potential synergistic fruits with ALDHI activity which could be explored alongside PJ: apple, mango, watermelon, papaya (potency: 76%, 62%, 57%, 50%)

Pomegranate is the best option so far because it's been verified to work and has other beneficial enzyme inhibition effects. I didn't mention nutmeg because it's a touchy subject.

 

[Ismene2]

You tried creatine? It just gives the brain much more energy and sharper cognition - really incredible effect with shrooms and acid.

 

[Allylbenzene]

You tried creatine? It just gives the brain much more energy and sharper cognition - really incredible effect with shrooms and acid.

Yes it's a great mitochondrial enhancer. (Mitochondria are what make cells work properly)
A few OTC things do the same thing...eg niacinamide, aspirin/salicylic acid, succinic acid, pregnenolone, coenzyme Q10, glucose, caffeine.

I can't help but think that MORE mescaline will result in higher plasma levels OF mescaline in a dose-dependent manner.

The goal isn't to increase plasma levels of mescaline.
The goal is to facilitate the formation of it's active metabolites.

 

[4DQSAR]

The goal is to facilitate the formation of it's active metabolites.

Mescaline IS active. I'm pretty sure there is quite a lot of evidence on that point.

 

[Allylbenzene]

Mescaline IS active. I'm pretty sure there is quite a lot of evidence on that point.

It does seem that way doesn't it. It's activity is perfectly compatible with it acting as an "active prodrug".

 

[4DQSAR]

It does seem that way doesn't it. It's activity is perfectly compatible with it acting as an "active prodrug".

Well, it's impossible to prove a negative but Hitchen's Razor applies.

 

[username_required]

It does seem that way doesn't it. It's activity is perfectly compatible with it acting as an "active prodrug".

Couldn’t literally every single active substance be described in the same way? This seems like an incredibly broad statement that has no actual meaning

 

[red22]

Mescaline IS active. I'm pretty sure there is quite a lot of evidence on that point.

Because [mescaline] was so weak and so upsetting to the subject's gastrointestinal tract, Alexander Shulgin modified the molecule in the 1960s, resulting in a whole family of popular street drugs that are still making the rounds of the U.S. underground. These include TMA, the amphetamine derivatives of mescaline, MDMA (Ecstasy), DOET, and DOM (see figure 12.1). As with the amphetamines themselves, these agents could (in low doses) enhance self-awareness and euphoria and produce visual distortions or hallucinations, or (in higher doses) blow the top off the mind. The increased potency of these synthetic drugs was due to the addition of the methyl group, which impedes enzymatic attack on the molecules. In fact, DOM's popularity among the California hippies was due to its extremely long-lasting action. They called it STP, for serenity, tranquillity, and peace.

The Dream Drugstore: Chemically Altered States of Consciousness. J. Allan Hobson. 2001. 15. From Cult to Laboratory: Mushrooms, Cactus Buttons, and Coca Leaves


This write up of mine provides some insight:

Did you know that an alternate name for mescaline is trimethoxyphenethylamine? Did you know that mescaline is similar to alpha-methylphenethylamine (more commonly known as amphetamine)? Did you know that beta-phenethylamine is the body's own version of amphetamine, and that if ingested, it doesn't work without an MAOI? And did you know that mescaline has a poor bioavailability because it is vulnerable to enzymatic attack, and that there is a synthetic analog called trimethoxyamphetamine that has a methyl group that impedes this enzymatic attack, thus giving it better bioavailability? Do you see a connection?

trimethoxyphenethylamine || beta-phenethylamine || 

trimethoxyamphetamine || amphetamine

The phens have poor bioavailabilities, but the amps have good bioavailabilities. Beta-phen does have a good bioavailability with an MAOI (making it like the speed version of ayahuasca). So, the creation of TMA is similar to the ayahuasca brew (it is a phen with a methyl group, and ayahuasca is basically a tryptamine with an MAOI). TMA can also be compared to psilocybin, while mescaline can be compared to DMT.


And these are relevant posts from another topic:

I think the running theory is that there is MAO in the gut and that it can be "overwhelmed" with enough NN DMT.....some speculate the same is true with oral dosage, albeit an even higher amount is required. The neurosoup girl used 600 mg of the freebase, dissolved in melted butter (so as it aint soluble in water and no one wants non polar solvents up the ass (even butter might be a stretch for some ) and had a hell of a trip. Long ago it was postulated that a similiar mechanism may be at work with mescaline, ie enzymatic or whatever activity in the body that because of the 2 carbon 3,4,5 pattern we encounter in nature our body has a limited ability to break this down, but once we get over around 200 mg of mescaline we are "overwhelmed" and the drug becomes active, which does correspond to the relatively steep does response curve above this amount. *warning* while this "speculation" wasnt conceived over bong hits it may well have been, i remember this idea being tossed around years ago but i dont believe there is anything but anecdotal evidence to support.....but back to the shamanic colonic....

^ That would imply that the dose of mescaline needed by injection would be a hell of a lot less, but as far as I know, the IM dose of mescaline isn't much less than the oral dose.

The 3,4,5-trimethoxy substitution probably allows the mescaline molecule to fit into the active site of MAO, but doesn't allow it to change to active conformation. 2,4,5-THPEA is inactive orally, so it would seem that the 4,5-dimethoxy groups need to have the 3 position free to be metabolized by MAO (3-methoxy-4,5-methylenedioxy is supposedly active at around the 250mg mark, but doesn't produce it's unique effects until 400-500mg). That in comparison to 3,4-methylenedioxyPEA, which is also inactive orally (same thing as the 4,5-dimethoxy groups of 2,4,5-TMPEA).

Other than the 3,4,5-trisubstitution pattern, the 2,4,5-pattern compounds are active if the oxygen on the 4 position (the methoxy group) is replaced by another atom, such as chlorine or carbon (methyl group). The 2C-T-x series exert a significant MAOI activity because of the similarity between the oxygen and sulphur atoms. The S of methylthio group interacts with the active site in the same way oxygen does, but prevents change to the active conformation of the enzyme. Not only does it do this, but it refuses to get out of the active site, so effectively inhibiting the enzyme

 

[Allylbenzene]

Mescaline IS active. I'm pretty sure there is quite a lot of evidence on that point.

It does seem that way doesn't it. It's activity is perfectly compatible with it acting as an "active prodrug".

Couldn’t literally every single active substance be described in the same way? This seems like an incredibly broad statement that has no actual meaning

He made the statement that mescaline is active. I agree, and further state that it also acts as a prodrug. Since he's pretty knowledgeable about drug metabolism I clarified that it was an "active prodrug" because many prodrugs are inactive. If I'd just called mescaline a prodrug that would have contradicted his statement.

 

[Ismene2]

The only other thing I might suggest is pregnenolone. Its the mother hormone but I noticed a subtle but powerful effect on colour perception. I've read a few people saying they've noticed it sober - so do I. I remember looking at the trees on pregnenolone and thinking wtf are all these colours? I went home and looked online and found out it does enhance colour.

I really notice it on acid so its worth checking out for mescaline.

 

[Allylbenzene]

The only other thing I might suggest is pregnenolone. Its the mother hormone but I noticed a subtle but powerful effect on colour perception. I've read a few people saying they've noticed it sober - so do I. I remember looking at the trees on pregnenolone and thinking wtf are all these colours? I went home and looked online and found out it does enhance colour.

I really notice it on acid so its worth checking out for mescaline.

Yes, it'll work well for mescaline... and everything really. I mentioned it on your christmas wishlist over on your thread. Not everyone will understand when you say it's the mother hormone but this picture should make sense to most people.

 

[4DQSAR]

He made the statement that mescaline is active. I agree, and further state that it also acts as a prodrug. Since he's pretty knowledgeable about drug metabolism I clarified that it was an "active prodrug" because many prodrugs are inactive. If I'd just called mescaline a prodrug that would have contradicted his statement.

I did contadict your HYPOTHESIS. I then asserted the in such cases, Hitchen's Razor is applied.

 

[Allylbenzene]

I did contadict your HYPOTHESIS.

You said mescaline is active which I'd agree with. The fact that mescaline is itself active is compatible with it producing active metabolites downstream (which are neither the aldehyde, acid or alcohol). Many active drugs produce active metabolites.

I then asserted the in such cases, Hitchen's Razor is applied.

Right. Well now there exists a suitable guide which allows people to see for themselves. Till now this notion has only been discussed on an old forum where it was rediscovered in 2011 and then confirmed. Since academia assumes there's nothing to see (because everyone knows that mescaline IS active) it won't bother looking.

 

[red22]

You said mescaline is active which I'd agree with.

And in contrast you feel that ergine is not psychedelically active … because of one, single utterly dismissive statement from Shulgin that begins with "this is an active compound" and ends with "probably correctly dismissed as not being a contributor". What a brilliant comment. It's not only not psychedelic, it's not even a contributor.

Do you realize that Albert Hofmann referred to ergine as "psychotomimetic"? Do you realize that he specified that the sedative effect was just one component of the effect:

"The hallucinogenic effect is also qualitatively different: it is characterized by a narcotic component."

All the relevant references as well as additional quotes about pure ergine from the 50s and 60s can be found in the topic that I created that features your argument: https://www.bluelight.org/community/threads/i-want-someone-to-analyze-this-argument.949614/ Also refer to my rebuttals to your beloved clavines: post-16313166, post-16323815

For anyone who isn't following, Allylbenzene feels that lysergic acid amide (ergine) is not a contributor to the action of morning glory seeds. He feels this way because Shulgin published a statement in TiHKAL stating that. That statement was stupid. Shulgin had done more psychedelics than Albert Hofmann, but one psychedelic he didn't do was lysergic acid amide. Allylbenzene knows that Shulgin didn't try lysergic acid amide and he knows that Hofmann did. Allylbenzene feels that "not a contributor" is an accurate summary of the effect of lysergic acid amide. For anyone who wants to see various quotes about the effects of lysergic acid amide from the 50s and 60s, see the topic that I previously mentioned, 949614.


"It appears that the agents that are responsible for the human activity of these plants are ergine and isoergine, and possibly the corresponding α-hydroxyethylamides of lysergic acid which could serve as metabolic precursors." –Alexander Shulgin

Psychotomimetic Agents by Alexander Shulgin. [Medicinal Chemistry: A Series of Monographs, vol. 4: Use, misuse, and abuse of psychopharmacological agents. Gordon Maxwell, ed., 1976. New York, NY: Academic Press Inc. pages 70-75. Lysergamides from the Convolvulaceae spp. / 2. PHARMACOLOGY]