Science paper Ayahuasca Alters Structural Parameters of the Rat Aorta

Ayahuasca Alters Structural Parameters of the Rat Aorta

More pointers towards health problems associated with the continuous use of ayahuasca (in rats)

 

[Mechanism]

I cannot emphasize enough how absolutely UNREALISTIC it is to administer drugs in this extremely stable chronic fashion, and call it anything similar to ayahausca.

Good point! Running a marathon daily would slowly break down your connective tissue and eventually lead to injury. However, jogging a couple of miles every morning would do the opposite.

I think it's also noteworthy that elite cyclists that push themselves too hard can accumulate scar tissue in their hearts over time. However, a third of the population of the Netherlands gets around by bike every day and there doesn't seem to be an epidemic of myocardial fibrosis over there.

 

[Voidmatrix]

I didn't get to read the whole paper. But I'm curious, do they plan to do the same test but with just harmala containing plants and then again with just DMT? I ask because what if it's just one component of the brew that causes these aortic restructurings in mice hearts.
Another reason I ask is because what if it's the journey itself, or more, our physiological response to an intense experience; elevated heart rate, higher blood pressure could also be heavy on the heart when encountered often enough (as shown in medical literature), that is leading to these restructured parameters.
A lot of questions here. I feel that overall the research gives us a heads up, but is a ways away from what we may call conclusive.

One love

 

[Varallo]

I'm literally a barista.

F Y I

lol, but still!

@Varallo if you wish to 'counteract' these structural changes of the peripheral and central vascular system, you could perhaps look into taking up weight training or a little power lifting as a way to re-thicken(strengthen, stiffen) those vessels. I think in the scientific literature of this topic might be able to confim this.



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also,

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I don't know your scientific orientation, as in, whether you yourself are a scientist of this or that field whatever, or dedicated lay reader, or what, but for me, coming from a non-professional background (albeit pharmacological & neurobiological lay-readership, not cardiovascular at all though!), a research article like this leaves MANY MANY open questions. I don't have enough expertise in these matters to even begin understanding the basis and context of this research article, nor approve, or fully understand the conclusion.

I see it as more of a statement or conclusion, than a deep investigatory analysis of it's own, as it's insight is only a small additional detail on top of many other scientific insights from which it draws and is dependent upon. The integrity of this insight, or what the heck even, is difficult to assess without really percieving into the nature of the scientific grounds upon which it is built. I am not in THE DISCUSSION, of this scientific circle. There is a huge rift between me and these scientists. I can only TRUST in them. My level of discernment on the matter is not evem remotely capable of critical analysis. This is important because I believe many of us do truly share this position to some extent, as most of us reading this and passing it around will not be the professionals. Yet we also mis-interpret them, and the context in which they say things. We run away with conclusions. Even the research articles can run away with conclusions, especially when pressured to produce some specific, super hyper extremensively distilled conclusion creating a singularity of causality, when in reality everything affects everything in one way or another in a complex ecosystem, where there is never binary, only quantum planes of colorful dynamic complexity xD (jk)




that being said, I would love to get into this, just for fun and because i care. It's a very complex matter! I share your passion for these beautiful magical substances and love to see the culture of science elaborate upon them.

However personally, colloquially, non-professionally, I am just left with so many questions after having read this.

- First of all, the physiological history of the rats I would like to know more about. What is this baseline, against which we are contrasting our results? I just, would like to know more about the baseline, of these rats.

- I would also like to know more about the preparation and delivery methods of the 4 types administration they performed. Did i miss something? or was this ayahuasca in some sort of dropper bottle? iv? did they use isolate or full spectrum brew?

- I would like to know why they also chose to administer it the way they did (acute and 'chronic'). The "Drug" and "Experimental Procedure" paragraphs are extremely short. Maybe i'm mising something as again, i'm NOT a scientist, but the Experimental Procedure section is just so extremely crazy short with no references or mentions of any of the details. They must literally be omitting everything as implication or standard procedure, as this is intended for professional discourse. As such, I do not know what (or how anything what even the heknuggets) this route of administration for acute and 'chronic' (14 days only) was executed in more exact details.

(ranting, 2 paragraphs)
like, the way the body adapts to CHRONIC MAOI inhbition changes after a day, a week, month, two or three months. This is more of a topic apparent in psychiatric discourse, which deals with 'chronicness' a lot. However it is my personal understanding that anything chronic, IN GENERAL, is just, toxic. Ayahuasca is not a chronic anything. Not a chronic phenonmen, experience, metabolically not chronic etc. Even in daily use there is an ebb and flow. This is relevant to not only neurotransmitter balances, but also hormonal balances, and just, everything. the whole darn everything. we are talking MAOI which affects so many systems, which in turn affect systems. For instance, MAOI inhibits the metabolism of adrenaline/epinephrine, which affects muscular tone. Typically these neurotransmitters(actually a hormone as well) are a very 'spiky' and dynamic phenomena, not flood. I literally cannot even gather my questions and thoughts here. MAOI, especially chronic administration effects so many things, some of which the body adapts to more rapidly than others, like chronically elevated serotonin.

Chronic is never a peak dose either. Also peak doses are perhaps maximally active only 8hours long, within a 24 hour day, and *special note, the MAOI is only really present for 12-18 hours or so in the unsaturated body. Only of the thigns i'm saying here right now is that, the typical conditions of engagement with ayahuasca on an extreme level might be, on average like, one strong trip a day, habitually, which is NOT chronic. That is NOT the same as chronic administration over 24 hours, like you might see in a drip, or medications engineered to release stable levels of drug over a 24 hour period at 12 or 8 hour administration intervals. having one flood dose within every 24 hours, of which perhaps, the following 8 hours after the peak 8 hours your body is still affected, and then the last 8 hours of the 24 hour window your body is fully balanced out with respect to DMT and already mostly metabolizing away a lot fo the MAOI ~ makes a huge difference.

It's the same difference as blasting off on 40mg of DMT every hour, vs doing a steady drip of 40mg DMT/hr. they are completely different just... so different, i cannot begin.


-First exposure reactions and adaptations to Ayahuasca is very different from habitual exposure. Like, the first time you work out in the weights gym ever vs daily gym goer.

- Why were 2 weeks of time for investigating the cardiac slides chosen, one week? 1 month? 3 months? what is so critical about analyzing the tissues at exactly 2 weeks? How was that decision made, as opposed to having 500 rats and investigating their herts/vasculature across various dosing reigmens and across time. what would a 1 week or 3 month acute or chronically dosed heart look like. Isn't that trajectory or evolution relevant? I find especially with chronic phenomena, and especially those concerning elasticity, that longer timescales also matter as collagen in general in the body operates adaptationally on longer time scales.

-Is this the rats FIRST time encountering ayahuasca or tryptamines in general? what is the adaptation process of the body when exposed to these molecules FOR THE FIRST TIME. Just because you break muscles after a workout does not mean workouts make you weaker. Just because you have inflammation does not mean your are not healing. etc! the body is highly dynamic about these things. For example, for the longest time it seems to me that we understood inflammation to be just... BAD ~ whereas now our better understanding is that of a signaling process telling the body where to heal, for instance. There is a dynamic web of causality across systems and time to be aware of. What you see in one instance is not the whole story.


-I cannot emphasize enough how absolutely UNREALISTIC it is to administer drugs in this extremely stable chronic fashion, and call it anything similar to ayahausca. What is up with science and chronic administration. ayahuasca is not chronically administered. The topic of research is AYAHUASCA, not 'how do MAOI alkalids and dmt' damage vasculature when administred in a toxic way. ayahuasca is also a PHARMOKINETICKK phenomenon, psychichally as well as physically experienced. These matter...

-how could incraesed vagal tone after ayahuasca administration be affecting this experiment? How could altered adrenal, cortisol, and dopamine levels be affecting the muscles? we know that all these neurotransmitters are deeply involved with muscles in general, and all are affected when talking about ayahuasca, or 'ayahuasca'.

-this is the moment where you read not only the research article, but if you are not IN the scientific discourse, you also need to read literally all these references to cardiology and whatnot to even have a context within which to even start understanding anything, or drawing conclusions.

Just FYI this barista is severely lacking in any vascular scientific knowelge, which is acutally a more central topic to this article than even the fact that ayahuasca is being studied, as we are talking about ayhuasca's effect on the HEART (& vasculature in general), for which you must know a lot about the heart, which I do not. I am also not a scientist by any stretch of the imagination.



Title:
"Ayahuasca Alters Structural Parameters of the Rat Aorta"



what the heck even,
my puppy is calling me




mush love!

Ah, a very long post, I’ll do my best to address at least some of points raised. Just to clarify upfront, this is not my area of expertise, and some of the more technical aspects are beyond my knowledge. That said, as a researcher I read allot of papers albeit in an unrelated field, so here are my thoughts.

First, I agree that this paper represents only a small piece of the puzzle and leaves many questions unanswered. This is very normal for research that focuses on a very specific topic. The trick most researchers apply is to isolate variables, by doing so you can make clearer statements about correlations. However, this also means the broader context is often left out. In this case, while the study examines potential effects of ayahuasca in rats, it doesn’t attempt to provide a full picture of its safety or impact in humans. It’s a data point in the much larger discussion about whether psychedelics are as physically benign as they’re often portrayed. Reading up on the references is useful and fun, but it takes allot of time, to put things in perspective, to really understand the context most people need years of reading in a specific topic.

As for the use of rats as a model, the amount n=40 and time chosen between the administration and then looking at target structures, this is probably based, in case of the numbers on finding balance between statistics and ethics, and the time period of a week is to exclude the chance of finding effects that are unrelated (more time is more chance for other factors), a control is not necessary I guess because of the wealth of existing data on rats.
Although rats provide a valuable model, it’s good to know that the findings don’t necessarily translate perfectly to humans. Animal studies like this are an important first step, but not a final step.

Your critique of the study’s chronic administration model is an important one. Ayahuasca, as traditionally used, is typically, by most, taken episodically, Chronic administration, as seen in this study, but also as I mentioned earlier in the case of micro dosing or daily dosing is relatively new. While most studies show that psychedelics are relatively safe when used episodically, chronic use however may not have the same benign effects.

Regarding the broader implications, this study is a useful example that psychedelics have physiological effects that warrant further research. Much of the recent discourse around psychedelics has focused on their psychological and therapeutic potential, which is exciting, but it’s also good to not forget the physical (negative) effects.

So, I see this paper not as a definitive answer but as a data point that gives direction, nothing less and nothing more.

 

[Mechanism]

Hey guys, I just skimmed through the paper and I'm just wondering if I missed something here, because the conclusion says the following:

Acute ayahuasca administration (2–4 mL/kg) and
chronic administration of a lower ayahuasca dose (2 mL/kg)
did not significantly alter structural parameters of the rat aorta
but produced modifications on VSMCs and collagen and
elastic fibers, suggesting vascular remodeling.

So if I'm comprehending this correctly, there was some evidence of vascular remodeling from chronic low doses, but the actual shape of the aorta was only significantly affected by chronic high doses. The last paragraph of the conclusion states that their main concern is frequent and prolonged use of high doses.

... do they plan to do the same test but with just harmala containing plants and then again with just DMT? I ask because what if it's just one component of the brew that causes these aortic restructurings in mice hearts.

Great that you should ask! Because the paper states the following just before the conclusion:

Human studies suggest that the cardiovascular effects of
ayahuasca are produced mainly by DMT because this
compound significantly increases blood pressure and HR
after parenteral administration. 21–24 The cardiovascular effects
of DMT are related to the agonist action of this molecule on
5-HT2A receptors, known to be critical in the cardiovascular
system. 25–28

So they suspect that DMT is the culprit because it basically increases the mechanical stresses on your heart. They then go on to say that b-carbolines (these are the harmalas right?) are hypotensive (they lower blood pressure), which makes them unlikely to be the cause. But then they say this:

However, it is pos-
sible that the MAO inhibition produced by harmine after
ayahuasca administration could have influenced at least in
part the hypertensive effects described because ayahuasca
significantly increases the urinary excretion of the norepi-
nephrine metabolite normetanephrine, indicating an increase
in norepinephrine secretion. 3

So they're saying that harmalas might only be an issue because they enable DMT to take effect, which raises your blood pressure? So essentially they're saying it's the DMT and not the harmalas. EDIT: Actually, they may be referring to how MAO breaks down adrenaline. When fully inhibited the body may have trouble regulating adrenaline levels. But the culprit of the increased adrenaline secretion in the first place is still the DMT.

Conclusion of the conclusion: They're only worried about frequent use of high doses because of the mechanical stress it puts on the heart due to the psychological stress of the experience. Seems like acute (occasional) high doses and chronic low doses do not significantly affect the structure of your heart tissue. Also harmalas alone do not have this effect because they lower blood pressure.


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EDIT: Wow, the more I think about this the more I realize how messed up this study is. If you read the last page in its entirety, it's suggested that the increased mechanical stress on the heart is due to secretion of norepinephrine, which is released with epinephrine during the fight or flight response (adrenaline and noradrenaline).

Seems like the high dose rats were pretty much subjected to extreme psychological stress every day for 14 days then euthanized. I'm wondering if an experienced ayahuasca drinker would reach similar levels of stress during high dose sessions, since they would be able to understand beforehand what they're getting themselves into.