Study on Gut & Serotonin

[indigoaura]

Serotonin & the Gut

Interesting stuff with a lot of potential implications for MDMA use and recovery.

 

[AutoTripper]

That's interesting Indigo and not at all surprisng. It may be one factor causing difficulty coming off antidepressants, I exoect the meds would mask the extent of the impact the altered flora on the patient's mental and emotional state.

Gut dysbiosys is extremely common if not normal to some degree for most, owing to somany separate factors.

And it is directly linked to the mind and emotions, with observable personality changes in people.
I swore years ago that my abusive intake of not just MDMA, but everything else in those tablets- binders, impurities, additional substances etc, would unquestionably have been a constant onslaught against my own intestinal flora.

Together with the whole lifestyle of course of nutritional neglect, chlorinated water, poly drug use, insane sleep patterns (maybe more accurate to just call them "patterns" hehe ).

And I also experienced prolonged periods of diarrhoea when I was really neglecting my diet and sleep and just popping pills that's regularly as anything.

But maybe MDMA/ecstasy pills could cause a sudden gut flora disruption in users whose intestinal microflora constitution is already weak or moderately compromise and maybe in many people's case this effect triggers a cascade of internal changes resulting in long-term comedown with the intestinal flora being directly related at root.

I wonder now, because I'm not sure I have seen it discussed with any emphasis or indication in the long-term comedown thread, how much sufferers have actually identified and attempted to recognise a case of intestinal dysbiosis?

Just thinking Aloud and on-the-spot really I'm not asking questions for you to answer a such but there may be something to this. Well there's lots to it just a question of exactly what but certainly worth some thought and exploration.

 

[AutoTripper]

Also I have to wonder, what would be revealed if all different sorts of of drugs and psychoactive compounds particularly chemical in nature I mean were tested in this fashion to see how they influence gut flora because I think generally such chemicals will have a negative influence, just by nature.

 

[AutoTripper]

But another thought which just sprung to mind as I entered thinking mode- I was thinking about the prospect which still is yet to be confirmed of me taking my MDMA pills myself and whether this sparing use would have a noticeable effect on my own still far from Ideal gut Flora.

And then I wondered whether plugging the dose would mitigate these effects and I have to think that it would possibly do so by entering the bloodstream and bypassing the gut.

But then I had a crazy and potentially silly thought, wondering if somehow how it is the drug affecting serotonin production in the gut via action on the brain and nervous system which is bringing about the bacterial alteration?

I think this may be worth considering as well. Maybe that is how it is and it's obvious and I'm just catching on a bit late as usual. I don't mean it is at all black and white like so, just shooting ideas.

 

[hyroller]

maybe shafting a pill was a bad idea. but it made the comeup less intense, but I'll never know why I did not go biting another half pill just for kicks lol. a double-ish dose. it was an unremarkable night, though I will say the comedown was less heady.

 

[epic11]

No1:

You:

maybe shafting a pill was a bad idea. but it made the comeup less intense, but I'll never know why I did not go biting another half pill just for kicks lol. a double-ish dose. it was an unremarkable night, though I will say the comedown was less heady.

 

[Swim15]

Obviously no one can say for certain but I don’t think that MDMA would be *likely* to have a significant impact for most people.

Mostly because the serotonin being impacted is in the brain and not peripherally (as far as I know). Not to say this couldn’t have an effect or wouldn’t have any effect at all, just that I don’t think acute exposure would be enough to impact the mechanisms regulating axon terminals and gut flora populations. Repeated exposure/abuse I could see being fairly detrimental though

 

[Phobos]

Obviously no one can say for certain but I don’t think that MDMA would be *likely* to have a significant impact for most people.

Mostly because the serotonin being impacted is in the brain and not peripherally (as far as I know). Not to say this couldn’t have an effect or wouldn’t have any effect at all, just that I don’t think acute exposure would be enough to impact the mechanisms regulating axon terminals and gut flora populations. Repeated exposure/abuse I could see being fairly detrimental though

MDMA binds to any Serotonin transporter and receptor it finds, the gut has loads of them.
If you ever had nausea after ingesting MDMA, that was the drug binding to your 5HT3 receptors.

 

[swilow]

Isn't serotonin mainly concentrated in the gut?

Anyway, definitely a field of great potential. I've been reading more and more about the idea of using probiotics as 'psychobiotics' to directly manipulate neurotransmitters.

The future of psychobiotics

Evidence shows that microorganisms in the gut influence mental health.

www.apa.org

 

[Swim15]

MDMA binds to any Serotonin transporter and receptor it finds, the gut has loads of them.
If you ever had nausea after ingesting MDMA, that was the drug binding to your 5HT3 receptors.

Yeah true. I haven’t seen enough research on how much 5HT3 receptors are involved but nausea makes sense with agonism obviously. Never experienced it myself but I’m not sure there’s enough research to tell the scope of effects beyond that although I’m sure there are some

 

[Swim15]

Isn't serotonin mainly concentrated in the gut?

Anyway, definitely a field of great potential. I've been reading more and more about the idea of using probiotics as 'psychobiotics' to directly manipulate neurotransmitters.

The future of psychobiotics

Evidence shows that microorganisms in the gut influence mental health.

www.apa.org

Correct and psychobiotics is an incredibly interesting field

 

[Phobos]

Yeah true. I haven’t seen enough research on how much 5HT3 receptors are involved but nausea makes sense with agonism obviously. Never experienced it myself but I’m not sure there’s enough research to tell the scope of effects beyond that although I’m sure there are some

Alcohol also binds to 5HT3 receptors to give you nausea.

 

[fasterfb]

@indigoaura
Thanks for the link to the article. I think there is a lot of potential in including good gut health as part of MDMA harm reduction.
I for one, will be stocking up on greek yogurt and sauerkraut on my next grocery day lol. Couldn't hurt!
Cheers

 

[AutoTripper]

@indigoaura
Thanks for the link to the article. I think there is a lot of potential in including good gut health as part of MDMA harm reduction.
I for one, will be stocking up on greek yogurt and sauerkraut on my next grocery day lol. Couldn't hurt!
Cheers

Just make sure you get raw, unpasteurised sauerkraut. It is usually refrigerated. Otherwise virtually all of the healthy, living, colonising bacteria have been killed off by the pasteurisation process.

Still nice and tasty of course, but not an effective probiotic at all.

Also, equally beneficial and important, and some even argue more so, are prebiotics- foods which feed the healthy gut microflora. Ideally both of course.

Proper raw fermented probiotic foods and drinks are both pro and prebiotic, but it still pays dividends to include plenty of prebiotiic foods in your diet.

Wheat bran is one of the most effective ones actually. Plenty more too.

 

[Swim15]

Alcohol also binds to 5HT3 receptors to give you nausea.

I’m not so sure the science is specific on alcohol binding to the receptor but it definitely influences it. Alcohol could also be causing peripheral effects on the vagus nerve

 

[Swim15]

I’m not sure I’d say wheat bran is a great prebiotic but inulin is one of the best. Artichoke, digestive resistant starch, flax seed (ground), psyllium husk, açaí fiber, etc

 

[Phobos]

I’m not so sure the science is specific on alcohol binding to the receptor but it definitely influences it. Alcohol could also be causing peripheral effects on the vagus nerve

Ethanol is an agonist at 5HT3.
The 5HT3 receptor is structurally different from all other serotonin receptors, that's why it's the only one directly affected.

 

[Hilopsilo]

MDMA binds to any Serotonin transporter and receptor it finds, the gut has loads of them.
If you ever had nausea after ingesting MDMA, that was the drug binding to your 5HT3 receptors.

Could you expand on this?

I've only had nausea from MDMA 2 or 3 times, and only puked from it once.

Does more nausea mean that more of the MDMA bound to 5HT3 in the gut as opposed to XYZ other serotonin(s) in another place? What external factors influence this? possible impact on subjective effects (doubt theres enough research though)?

 

[Swim15]

Ethanol is an agonist at 5HT3.
The 5HT3 receptor is structurally different from all other serotonin receptors, that's why it's the only one directly affected.

I don’t think it is. Below is the only study I could find that talked about it at length and they said the interaction is still being delineated but that it does bind to receptor ion channels

The Role of 5-HT3 Receptors in Drug Abuse and as a Target for Pharmacotherapy

Alcohol and drug abuse continue to be a major public health problem in the United States and other industrialized nations. Extensive preclinical research indicates the mesolimbic dopamine (DA) pathway and associated regions mediate the rewarding and reinforcing ...

www.ncbi.nlm.nih.gov

 

[Swim15]

Could you expand on this?

I've only had nausea from MDMA 2 or 3 times, and only puked from it once.

Does more nausea mean that more of the MDMA bound to 5HT3 in the gut as opposed to XYZ other serotonin(s) in another place? What external factors influence this? possible impact on subjective effects (doubt theres enough research though)?

MDMA is an SRA - serotonin releasing agent. Really an SDRA. In addition, it’s also an SRI - serotonin reuptake inhibitor.

This means that’s it’s going to release and inhibit reuptake of 5HT at all serotonin receptors (I’m inferring a little bit from the science here), of which there are different types and subtypes.

I haven’t looked into this all that much but I would guess, based on other mechanisms in pharmacology, that this may be somewhat selective as the degree of release and reuptake inhibition could vary significantly at different receptors - especially based on subjective effects. I don’t know for sure though, someone may have some literature that talks about it.

As far as nausea with MDMA that’s one reason why I think it varies. Some people always get sick, some people do only sometimes, and some never do. I never do but I’ve got friends that puke on 180mg every time. Could also be due to contaminants as well though.