DMPEA potential neurotoxin in cacti

[burnt]

Browsing through the literature I came across a number of studies demonstrating that 3,4-dimethoxyphenylethylamine is a neurotoxin that kills dopamine neurons in the nigrostriatal system which may have implications for parkinsons disease.

A number of potent neurotoxins such as MPTP which is metabolized in MPP+ in the brain by MAO (a very potent neurotoxin that causes irreversable parkinsons symptoms in humans and animals) also have this effect.

Here is the study: http://www.sciencedirect.com/scienc...serid=10&md5=6ec2333af8d2f27fd96e1fa3e9199f12

This compound is found in a number of cacti such as peyote san pedro and peruvian torch. Although there is no indication that consumption of these cacti species can cause damage to neurons and cause parkinson like symptoms I think its worth noting. Purification of alkaloids from cacti without proper identification could lead to consumption of this substance. Although this substance has been administered to humans in Phikal and no effects were noted no one was looking at this neurotoxic effect. High levels of DMPEA has also been observed in the urine of patients with parkinsons.

I don't think there is any problem with consuming many cacti or mescaline in terms of neurotoxic effects but purifying these alkaloids, not identifying them, and consuming them is a potential risk as you may be ingesting this compound DMPEA.

I would like a more professional opinion on this. Too bad Ask Dr. Shulgin on line is shut down. I wonder if there is anyone we can consult about this?

 

[kyrolima]

Is The resin tek a danger?
Is the Limonene tek a danger?

 

[burnt]

No I doubt it. Like I said there is no evidence that eating cactus cases nerve damage in this part of the brain. So far all evidence points out that users of peyote do not have any kind of brain damage and sometimes they perform better in neurocognitive tests then non users.

The only risk that I can forsee is if someone deliberating concentrations other alkaloids in cacti in doses far higher then those normally found in the plant and takes it many times. But not much research has been done on this so I can't really say. Its why I'd like some more professional input.

Traditional preperations and usage are probably fine. Extracting mescaline is probably fine. But collecting tons of the "other" alkaloids, not identifying them, and consuming then could pose a risk if this substance is present in concentrations far higher then normally consumed.

 

[benzyme]

not a professional (more of a pharmacology/neurochem erudite) but it would seem that DMPEA is a short-lived metabolite.

it's hard to imagine something as destructive as MPP+, it's a VERY neurotoxic intermediate found in incomplete synthesis of a meperidine analogue. it shreds the dendrites and axons of D1 receptors in the substantia nigra, excitotoxicity extraordinaire. first time users can immediately get these parkinsonian-like symptoms. I remember reading about a heroin addict that botched a MPPP synthesis and basically turned into a vegetable because of him trying his tainted product.

 

['Coatl]

Burnt your saying it may be dangerous to extract individual compounds from cactus and take them in high amounts?

Not that cactus extracts or cactus itself could be dangerous, right?

 

[w0mbat]

Great find burnt

This is an important topic and warrants further investigation

I only had time to give the full article a quick read, but here are a few things worth noting:

-They directly injected DMPEA into rat brains, and the rats were infused continuously for a week. They did not look at oral ingestion.

-They looked at biochemical markers of dopamine metabolism, not at behavioral measures.

-They found that DMPEA inhibited mitochondrial complex I as well as other enzymes related to energy metabolism. From a theoretical standpoint, I believe it is the inhibition of Complex I that is most important to neurotoxicity. I could be wrong on this, but does this imply that taking CoQ supplements could counteract the neurotoxic effects of DMPEA?

However the most important question on my mind right now is how do we know DMPEA is even present in San Pedro / Peruvian torch? Do you have a source for this burnt?

And if DMPEA is present in San Pedro / P.Torch, does anyone have any idea how much?

If anyone else is interested in reading the full text of the article, let me know.

 

[۩]

This reminds me of that toxic chemical in mullein that scares people away from working with it every once and a while.
There has to be a reason why this DMPEA is in there if it is.
What temperature does DMPEA break down?

More fear projected onto these beloved teachers.

 

[benzyme]

it's there as an intermediate; there's probably an O-methyltransferase responsible for the conversion from dopamine.

methinks it's nothing to worry about, otherwise there would likely be case studies of the toxic side effects regarding the indigenous use of Trichocereus in native south american tribes.

 

[w0mbat]

True, it probably won't cause end-stage Parkinson's overnight. However IMO the potential for DMPEA to chip away at one's nigrostriatal neurons is a good reason to not use cactus. And for those who use it anyway, I think it's a good enough reason to take anti-oxidative measures before imbibing (i.e., aerobic exercise, anti-oxidant rich diet, and possibly CoQ supplementation).

If you like, you could consider it the modern analogue of the shamanic rituals of purification before embarking on an ayahuasca voyage...

 

[۩]

True, it probably won't cause end-stage Parkinson's overnight. However IMO the potential for DMPEA to chip away at one's nigrostriatal neurons is a good reason to not use cactus. And for those who use it anyway, I think it's a good enough reason to take anti-oxidative measures before imbibing (i.e., aerobic exercise, anti-oxidant rich diet, and possibly CoQ supplementation).

If you like, you could consider it the modern analogue of the shamanic rituals of purification before embarking on an ayahuasca voyage...

Of course...these are entheogens we are talking about here.
These cacti are extraordinarily complex, it seems. I think they already do take care of it themselves, as they are extremely purifying on all levels of this existence.
To be afraid of this medicine is...so ridiculous...

 

[antichode]

However IMO the potential for DMPEA to chip away at one's nigrostriatal neurons is a good reason to not use cactus.

This is crazy, be mindfull of a study and certain compounds yes, but lets not jump to wild conclusions. I think the potential for it to 'chip away' is quite unlikely. As you said before we dont know how much of this is in cactus, and there is no evidence that the minute amounts which could be present cause damage to humans when used recreationally.

Afterall, there are a lot of things that if injected into the brain for a week straight would cause no end of damage.

If this was a serious issue it would have popped up by now and some one would have drawn the line from disease to plant use as its got a very long history of use with little to no side effects noticed thus far.

its good to watch this space tho, and be mindful.... Eating cactus everyday should probably be avoided, but thats a no brainer

 

[endlessness]

True, it probably won't cause end-stage Parkinson's overnight. However IMO the potential for DMPEA to chip away at one's nigrostriatal neurons is a good reason to not use cactus. And for those who use it anyway, I think it's a good enough reason to take anti-oxidative measures before imbibing (i.e., aerobic exercise, anti-oxidant rich diet, and possibly CoQ supplementation).

If you like, you could consider it the modern analogue of the shamanic rituals of purification before embarking on an ayahuasca voyage...

Of course...these are entheogens we are talking about here.
These cacti are extraordinarily complex, it seems. I think they already do take care of it themselves, as they are extremely purifying on all levels of this existence.
To be afraid of this medicine is...so ridiculous...

well gotta disagree with you there, house...

I think its very understandable and reasonable to question about the possibility of adverse effects in long and short terms of the different substances we ingest.. This doesnt mean panicking or anything, but being open and incentivating new research that can enlighten us on these things.. For example, it could come to the attention that the other alkaloids present in these cactus protect the brain against the damage of DMPEA.. Or it could be found that these alkaloids would protect the brain, as long as such and such added ingredient is added to the brew.. or that it doesnt do any damage at all, or that its quite dangerous, or whatever..

There are many interesting possibilities and considering and researching about them does not mean disrespecting the medicine or whatever one calls it

 

[benzyme]

it could just be that DMPEA does not bind with the strong affinity that, say, MPP+ does. The latter is analagous to a neuroleptic irreversible inhibitor.

as long as receptors aren't subjected to such ligands, neuroplasticity is observed.

 

['Coatl]

True, it probably won't cause end-stage Parkinson's overnight. However IMO the potential for DMPEA to chip away at one's nigrostriatal neurons is a good reason to not use cactus. And for those who use it anyway, I think it's a good enough reason to take anti-oxidative measures before imbibing (i.e., aerobic exercise, anti-oxidant rich diet, and possibly CoQ supplementation).

Oh come on that is nuts!

We have studies done of both Lophophora and Trichocereus cacti that say they are safe, safe, SAFE!

Now if go messing around concentrating, synthesizing and extracting you may have something to worry about, but the cacti themselves have been PROVEN to be without a doubt SAFE!

 

[w0mbat]

it could just be that DMPEA does not bind with the strong affinity that, say, MPP+ does. The latter is analagous to a neuroleptic irreversible inhibitor.

I think it is not just a matter of affinity, also. DMPEA and MPP+ seemed to have different kinds of affects on dopamine biochemistry, too.

Attached is the full text of the article for those interested

 

[w0mbat]

This is crazy, be mindfull of a study and certain compounds yes, but lets not jump to wild conclusions. I think the potential for it to 'chip away' is quite unlikely. As you said before we dont know how much of this is in cactus, and there is no evidence that the minute amounts which could be present cause damage to humans when used recreationally.

All i meant is that if someone told me that they didn't want to try cactus because of the possibility of neurotoxicity, I wouldn't think they were an idiot. Indication of harm is all that should be necessary for action, not proof of harm.

The idea of DMPEA "chipping away" at dopaminergic neurons goes like this: in your brain, there are a bunch of neurons in one area that make dopamine for the rest of the neurons in your brain. You are born with only a limited number of them, and they die off normally through life. When you lose enough, you start to get symptoms of what we have termed "Parkinson's disease". While most people die before enough of their dopamine-producing neurons are lost to cause PD, the rate of loss can be affected by the things one does during their lifetime (such as exposing oneself to chemicals that cause dopaminergic neuron degeneration). Hence, over-exposure to some chemicals early in life could lessen one's "neuronal reserve," and make someone who would have died of, say, a heart attack, come down with PD later in life and die of that instead.

Even if San Pedro / P. Torch do contain DMPEA, and even if it is neurotoxic in the way we fear, using these cacti would not cause PD symptoms overnight. We're talking about consequences that would manifest at the other end of the lifespan.

Afterall, there are a lot of things that if injected into the brain for a week straight would cause no end of damage.

Well, they did do a saline control FWIW. Another study I came across* also found neurotoxicity in cell cultures.


*Here's the citation:
Brain Research 754 (1997) 260–268
Neurotoxic effects of papaverine, tetrahydropapaverine and dimethoxyphenylethylamine on dopaminergic neurons in ventral mesencephalic-striatal co-culture
Keigo Goto, Hideki Mochizuki, Tastuya Hattori, Noriyuki Nakamura, Yoshikuni Mizuno

 

[benzyme]

MPP+ is a cationic beast.
look at the substantia nigra cell reduction comparison in Fig. 1 :shock:

administer L-DOPA and Rasagiline.

 

[antichode]

Indication of harm is all that should be necessary for action, not proof of harm.

Yeah your right, and its very alarming.... SWIM thought he'd found something that he could happily work with, confident in the knowledge that no harm could possibly be done. He realy does hope that more studies are done on these compounds.

Has dmt mescaline, psilocybin etc been put through similar testing?

 

[burnt]

Again I think its highly unlikely that consuming cacti themselves at normal doses at a schedule similar to that of members of native american churches is harmful. There is no indication that these people have higher incidences of parkinsons. If they did I am sure someone would have noticed and used it as a tool to try and ban peyote even more.

I don't know what levels DMPEA is found in cacti but it is found in all the main species according to thikal's big list at the end. I've seen some literature reports were its identified but I forget where I found those. Anyway it seems the damage is specifically associated with 3,4 methoxy substitutions (so don't worry about other psychedelics like mescaline they don't have this effect). Also yes in the study they were directly infusing the stuff into the rat brain. Its very possible that this stuff is quickly metabolized before it can cause any harm in humans especially at concentrations normally found in cacti.

The only possible area where I could see this ever being a problem is if someone purified the compound unknowingly by separating the other non mescaline alkaloids and experimenting with them in high doses many times. If it contained DMPEA you might not notice because its not psychoactive. Also this compound has been consumed by humans (phikal) and didn't cause any acute noticable damage. But chronic use could who knows. However no one would chronically use an inactive substance unless it was mixed with another substance and they didn't realize it.

I really don't think there is anything to worry about but its worth noting. I think consuming extracted mescaline and cacti is fine. I am going to go through the literature a bit on some of the pharmacology of the other alkaloids to try and determine how safe they are and what is known. I can't find much more on DMPEA.

Yes the MPP+ is way more neurotoxic in all these studies. Its a well known compound by now thats used to purposely cause damage to dopamine system when researching potential cures of parksinsons. I feel bad for the poor folks who got that batch of bad opiates.

 

[kemist]

There is no problem with traditional use indeed.

But how about limonene tek? Not traditional at all, is it?

ILPT bet his parrot that during basifying with calcium hydroxide at least one alkaloid in mixture decompose.
He can smell dying alkaloid when mixing water-cacti-calc mix.
What if swimmer creating some toxic shit and then extracting it without even realizing that ?