Self-experiment with Montelukast for repairing brain damage

[Monty79]

Hi all,

many years ago I experienced psychosis from MDMA abuse from which I came out after about 1 year, but anxiety and sometimes depression never went away fully. Also I had to be extremely careful about what substances I took ever since, for example only traces of tryptophan or St John's wort will act like a psychoactive substance for me (with a terrible hangover/depression the next day). I guess my blood-brain-barrier is damaged.

Last year I came across this article on reddit:
https://www.newscientist.com/articl...venated-and-new-neurons-grown-by-asthma-drug/

This drug is a harmless asthma medication GP's are prescribing even to kids or for hay fever, so I was thinking to myself if it doesn't help it won't do much harm. 5 days ago I started my little self-experiment with 10mg montelukast daily. I'm feeling great so far, a bit funny sometimes, but no anxiety or depression, just a slight headache but not too bad, enough to notice there's something going on in my head, lol.

If some of you guys are interested I will update, I'm planning on making the ultimate tryptophan challenge in about 2 months which will show if there's some improvement in my bbb.

I would be very interested in hearing your thoughts or questions if there are any.

 

[Monty79]

Yes, it was more ecstasy/molly overuse.

And yes, I do know tryptophan is part of milk and meat which I do consume without any problems. What's causing me to trip is the l-tryptophan form as a supplement, and I have no explanation for it other than my bbb is damaged. I'm not talking about feeling a bit off, those substances are sending me on a full-blown psychoactive trip. Tryptophan and St John's wort were just examples, there are many others I have to be very careful about.

No, I haven't tried N-acetyl-L-cysteine yet, thanks a lot for the tip. I will look into it.

I don't have hay fever symptoms, I just mentioned montelukast is prescribed for hay fever symptoms for getting the point across how harmless this drug is.

I do not think you are going to find many people on here using it for the same purpose as you. The data simply isn't there,

I'm aware of this, that's why it's called a self-experiment.

Thanks for your reply.

 

[Wiserthanearlier]

Its certainly very interesting, ill watch this thread. Thanks

 

[Monty79]

Regarding your B-B-B being damaged, I don't know, man. I think this is more of an all-encompassing system that is active at all times, rather than a specific organ so to speak. Although there are drugs known to damage it/increase its permeability over time (think, methamphetamine, low-calorie/undernuourished diets, etc)

What kind of active system do you think could cause my oversensitivity to those substances? I'm certainly open to other kinds of explanations, a damaged bbb was just what made the most sense that I could find.

 

[Cotcha Yankinov]

There are also portions of the brain that aren't protected by the BBB. There could be dysfunction in those areas, and there would be no need to invoke a dysfunctional BBB as an explanation

 

[Monty79]

There are also portions of the brain that aren't protected by the BBB. There could be dysfunction in those areas, and there would be no need to invoke a dysfunctional BBB as an explanation

In your opinion how would that scenario explain the oversensitivity that I'm experiencing?

 

[Cotcha Yankinov]

One scenario is that there are upregulated post-synaptic serotonin receptors in the relevant unprotected areas due to decreased pre-synaptic release of serotonin, and these areas are then sensitive to the increase in peripheral 5-HT after taking 5-HTP.

MDMA users have been found to have upregulated 5-HT2A receptors (a post synaptic receptor) in some areas and this can be taken as a sign of decreased pre-synaptic release of serotonin.

Although 5-HTP can cause MDMA-naive people issues as well.

Edit: I should point out (now that I see you are sensitive to tryptophan) that tryptophan should actually increase serotonin in the entire brain, so we need no real explanation involving the BBB it seems like.

 

[serotonin2A]

^Ingesting tryptophan doesn't change serotonin levels in the brain unless you are malnourished. The transporter that brings tryptophan into the brain transports other amino acids, so increasing plasma tryptophan levels alone does not appreciably raise tryptophan levels in the brain because there is competition with other amino acids. Furthermore, the activity of tryptophan hydroxylase (the enzyme in the brain that converts tryptophan to 5-HTP) is rate-limiting and heavily regulated, so even if you manage to raise tryptophan levels in the brain above normal concentrations, neurons will only hydroxylate it to a limited extent.

 

[Monty79]

Thanks for your reply.

Furthermore, the activity of tryptophan hydroxylase (the enzyme in the brain that converts tryptophan to 5-HTP) is rate-limiting and heavily regulated, so even if you manage to raise tryptophan levels in the brain above normal concentrations, neurons will only hydroxylate it to a limited extent.

I'm not sure if I understand what this means in relation to my oversensitivity. If it's not possible to raise tryptophan levels in the brain and my neurons shouldn't hydroxilate it in the first place, why do I have such an intense reaction to it?

Until now I'm still only left with the explanation about the bbb, nothing else makes sense to me so far. Turns out there is indeed evidence ectsasy may be causing damage to the bbb.
https://www.newscientist.com/article/dn8314-ecstasy-may-damage-the-brains-physical-defences/

I will stick to my little experiment and report back in a few weeks. So far I'm feeling great, really great...

 

[Cotcha Yankinov]

^Ingesting tryptophan doesn't change serotonin levels in the brain unless you are malnourished.

But what's the deal with L-tryptophan's supposed effects on sleep?

https://www.ncbi.nlm.nih.gov/pubmed/6764927
https://www.ncbi.nlm.nih.gov/pubmed/91481
https://www.ncbi.nlm.nih.gov/pubmed/227180

Since people with the short allele at 5-HTTLPR are thought to be vulnerable to tryptophan depletion, I'd be curious what the timeline is on tryptophan depletion -> symptoms.

There is also some evidence that people with the short allele also have more adverse effects after MDMA, and those short allele MDMA users perform similarly to controls undergoing tryptophan deprivation, so we might be dealing with a unique situation here.

The transporter that brings tryptophan into the brain transports other amino acids, so increasing plasma tryptophan levels alone does not appreciably raise tryptophan levels in the brain because there is competition with other amino acids.

I'm confused, shouldn't there be more tryptophan uptake without the other amino acids competing for that transporter? Or does protein intake increase the function/expression of the transporter?

Furthermore, the activity of tryptophan hydroxylase (the enzyme in the brain that converts tryptophan to 5-HTP) is rate-limiting and heavily regulated, so even if you manage to raise tryptophan levels in the brain above normal concentrations, neurons will only hydroxylate it to a limited extent.

Isn't serotonin synthesis a bit dynamic and could be expected to be abnormal in an MDMA-adverse effects sufferer, or someone with depression?

https://www.ncbi.nlm.nih.gov/pubmed/23325232

"Dynamic serotonin biosynthesis is important for serotonin function; however, the mechanisms that underlie experience-dependent transcriptional regulation of the rate-limiting serotonin biosynthetic enzyme tryptophan hydroxylase (TPH) are poorly understood.

Here, we characterize the molecular and cellular mechanisms that regulate increased transcription of Caenorhabditis elegans tph-1 in a pair of serotonergic neurons ADF during an aversive experience with pathogenic bacteria, a common environmental peril for worms.

Together, our work elucidates the molecular and cellular mechanisms whereby experience modulates tph-1 transcription."

 

[serotonin2A]

Thanks for your reply.
I'm not sure if I understand what this means in relation to my oversensitivity. If it's not possible to raise tryptophan levels in the brain and my neurons shouldn't hydroxilate it in the first place, why do I have such an intense reaction to it?

Until now I'm still only left with the explanation about the bbb, nothing else makes sense to me so far. Turns out there is indeed evidence ectsasy may be causing damage to the bbb.
https://www.newscientist.com/article/dn8314-ecstasy-may-damage-the-brains-physical-defences/

I will stick to my little experiment and report back in a few weeks. So far I'm feeling great, really great...

The simplest explanation is that you have an immune reaction (allergy) to high levels of tryptophan. Some people exhibit reactions to chemicals that are normally well tolerated. It is possible for someone to be allergic to tryptophan, but that doesn't mean that the reaction has anything to do with serotonin in the brain. This possibility actually fits rather well with your experiment, because SINGULAIR is a drug that blocks allergic reactions.

But one question that comes to mind is how have you determined that you are hypersensitive to tryptophan? You would have to take pure tryptophan to know that you are hypersensitive to it, but that is very difficult these days because the pure compound has been pulled off the shelves in most countries due to EMS syndrome. Even if you are able to buy tryptophan somewhere as a supplement, you are not taking tryptophan alone -- it is mixed with various other binders when pills or tablets are prepared, and you might be reacting to one of those excipients, or to a containment (that is what killed people via EMS). Unfortunately, it is also common to find that dietary supplements are completely mislabeled, so you might be taking something completely different.

EDIT: As I noted in my other post, tryptophan is also metabolized to kynurenic acid, so that is yet another possible mediator of the reaction you are having (if it is indeed due to tryptophan). So there are many possible explainations for hypersensitivity (fillers, contaminents, allergy, peripheral metabolites)...I don't se any reason to think this is related to central serotonin or the BBB, which are highly unlikely (and would be causing other obvious problems).

 

[serotonin2A]

But what's the deal with L-tryptophan's supposed effects on sleep?

https://www.ncbi.nlm.nih.gov/pubmed/6764927
https://www.ncbi.nlm.nih.gov/pubmed/91481
https://www.ncbi.nlm.nih.gov/pubmed/227180

Tryptophan is metabolized to kynurenic acid...someone who ingests large amounts of tryptophan will probably increase kynurenic acid levels. That is just a guess, but it is a huge assumption to link any effects of tryptophan to serotonin.

Since people with the short allele at 5-HTTLPR are thought to be vulnerable to tryptophan depletion, I'd be curious what the timeline is on tryptophan depletion -> symptoms.

There is also some evidence that people with the short allele also have more adverse effects after MDMA, and those short allele MDMA users perform similarly to controls undergoing tryptophan deprivation, so we might be dealing with a unique situation here.

Sorry, I'm not totally following why you brought up tryptophan depletion? Tryptophan depletion and tryptophan loading are completely different issues. It is entirely possible to deplete brain serotonin by removing dietary tryptophan, but that doesn't mean you can push the system in the opposite direction by loading up on tryptophan.

I'm confused, shouldn't there be more tryptophan uptake without the other amino acids competing for that transporter? Or does protein intake increase the function/expression of the transporter?

A normal person who isn't malnourished will have amino acids in their blood and those will compete for access to the amino acid transporter. So there are other amino acids competing for transport.

Isn't serotonin synthesis a bit dynamic and could be expected to be abnormal in an MDMA-adverse effects sufferer, or someone with depression?

Yes, tryptophan hydroxylase levels are regulated and can increase or decrease, but I don't see how that is relevant here, because what changes is not how TPH is regulated, but rather the amount of regulation. So in any event a manipulation that increases 5-HT levels above normal is going to inhibit TPH. If you are talking about the possibility that patients are tryptophan deficient, then tryptophan loading would be restoring their 5-HT levels to normal, which is a different situation then using tryptophan loading to elevate 5-HT levels above normal levels.

 

[Cotcha Yankinov]

Re: tryptophan depletion, I was curious how long it would take before tryptophan depletion would start to affect someone who was vulnerable because I assumed that once they were affected by the tryptophan deprivation, tryptophan supplementation might push them beyond baseline for a little bit.

Let's say there is some amount of TPH upregulation and receptor upregulation to compensate for reduced tryptophan - surely that can't compensate completely for tryptophan depletion, otherwise people would have no symptoms with tryptophan depletion. Therefore, I was thinking there might be a small window where you have restored tryptophan but still upregulated receptors and TPH.

But I'm fuzzy on the timelines there, maybe the receptors/TPH downregulate so fast that it can't account for the OP's experiences (I see now that they get "psychoactive effects"?)

Sorry I thought this was just about anxiety induced by 5-HTP type stuff, which I've heard of a lot from people who have problems after MDMA.

 

[serotonin2A]

Re: tryptophan depletion, I was curious how long it would take before tryptophan depletion would start to affect someone who was vulnerable because I assumed that once they were affected by the tryptophan deprivation, tryptophan supplementation might push them beyond baseline for a little bit.

Let's say there is some amount of TPH upregulation and receptor upregulation to compensate for reduced tryptophan - surely that can't compensate completely for tryptophan depletion, otherwise people would have no symptoms with tryptophan depletion. Therefore, I was thinking there might be a small window where you have restored tryptophan but still upregulated receptors and TPH.

But I'm fuzzy on the timelines there, maybe the receptors/TPH downregulate so fast that it can't account for the OP's experiences (I see now that they get "psychoactive effects"?)

Sorry I thought this was just about anxiety induced by 5-HTP type stuff, which I've heard of a lot from people who have problems after MDMA.

5-HTP is a completely different compound -- it is possible to raise central 5-HT levels by ingesting 5-HTP.

 

[Monty79]

But one question that comes to mind is how have you determined that you are hypersensitive to tryptophan? You would have to take pure tryptophan to know that you are hypersensitive to it, but that is very difficult these days because the pure compound has been pulled off the shelves in most countries due to EMS syndrome. Even if you are able to buy tryptophan somewhere as a supplement, you are not taking tryptophan alone -- it is mixed with various other binders when pills or tablets are prepared, and you might be reacting to one of those excipients, or to a containment (that is what killed people via EMS). Unfortunately, it is also common to find that dietary supplements are completely mislabeled, so you might be taking something completely different.

I have this product and I think it is indeed pure l-tryptophan:
http://www.zeinpharma.com/l-tryptophan-capsules

But, please, as I already mentioned above, don't focus only on tryptophan as I am having this hypersensitivity reaction to A LOT of other medications and substances! St John's wort is one of them, actually all that are in the direction of being psychoactive. I wouldn't even try 5-HTP as a supplement as I know what it would cause. If I took just ONE pill of a SSRI it would send me on a horror trip that would be horrendous! (ANXIETY for days!)

I'm very sensitive to pain medication as well, or a valium pill would knock me out for a whole day!

That's the reason why I'm so sure the bbb is involved here, please don't concentrate on tryptophan alone.

I don't se any reason to think this is related to central serotonin or the BBB, which are highly unlikely (and would be causing other obvious problems).

What kind of other obvious problems could those be if I may ask?

 

[Cotcha Yankinov]

"Can somebody be allergic to serotonine alone? Huhh? Uhm no... ?"

The possibility that Serotonin2A has suggested wherein you are having an immune reaction to a filler and such in the various pills could explain a similar reaction across supplements, if similar fillers are used. So it wouldn't necessarily be an allergy to serotonin, just an allergy to the packing of the supplement/medication.

I don't necessarily think a strong reaction to pain killers and benzos are out of the ordinary by the way, I mean they are very strong drugs to those without tolerance.

 

[serotonin2A]

I have this product and I think it is indeed pure l-tryptophan:
http://www.zeinpharma.com/l-tryptophan-capsules

But, please, as I already mentioned above, don't focus only on tryptophan as I am having this hypersensitivity reaction to A LOT of other medications and substances! St John's wort is one of them, actually all that are in the direction of being psychoactive. I wouldn't even try 5-HTP as a supplement as I know what it would cause. If I took just ONE pill of a SSRI it would send me on a horror trip that would be horrendous! (ANXIETY for days!)

I'm very sensitive to pain medication as well, or a valium pill would knock me out for a whole day!

That's the reason why I'm so sure the bbb is involved here, please don't concentrate on tryptophan alone.

What kind of other obvious problems could those be if I may ask?

Just to be clear, the product is not pure tryptophan. It also contains gelatin, magnesium salts from fatty acids, titanium dioxide (ingredients listed on the label). The thing is, it undoubtedly contains other ingredients, because when they make capsules and fill them they have to use lubricated molds and you could be allergic to the lubricant.

I'm not sure why you have linked your symptoms to the BBB but the symptoms you are having are not consistant with BBB dysfunction. Typical symptoms of acute BBB dysfunction include seizures and severe neurological impairement. In addition to large amounts of serotonin, blood contains amino acids such as glutamate and aspartate that act as excitotoxins in the brain. Think about what would happen if those peripheral chemicals were not kept out of the brain. If your main symptom is hypersensitivity to many types of drugs then that is not likely to reflect BBB impairement -- most drugs are perfectly capable of reaching the brain.