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Comment by FollowingTheDao | Hacker News Reader

I cannot even eat food high in trace amines or I get anxious as all get out and I am up all night. Seriously, chocolate gives me insomnia. So I have no idea how someone could handle these drugs.

I think this happens to me for two reasons. I am low in BH4 which limits my ability to metabolize amino acids down the common pathway and thinks like phenylalanine get metabolized dow the alternative pathways creating PEA and Tyramine. But also I have the mental illness associated changes in TAAR1 and VMAT1 and VMAT2. (I have schizoaffective Bipolar Disorder.)

I never understood why people would want to take drugs to see the shit and live the suffering I have all my life but that's where we are...

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"I never understood why people would want to take drugs to see the shit and live the suffering I have all my life but that's where we are..."

MDMA helped this man with aspergers: [1]

And here is a woman talking about how psilocybin helped her cope with cancer-related depression: [2]

Finally, here is a "normal" woman talking about her experiences on LSD: [3]

Hopefully this will give you some insight in to why people take psychedelics.

[1] - https://www.youtube.com/watch?v=PJgWKl_vss0

[2] - https://www.youtube.com/watch?v=us7qLnTPhiI

[3] - https://www.youtube.com/watch?v=Si-jQeWSDKc

[1] - That video was interesting since I know MDMA has a strong effect on norepinephrine and I have had that same experience of calm taking clonidine which stimulates the a2 receptors. I have a similar experience to Larry and therapists have said in the past I have Asperger's. I am low on the classic catecholamines so this makes sense.

[2] - It is normal to be depressed when you have cancer so I have no opinion on that. To me that is something I work through cognitively. I would never tells someone not to take it though because if you have never done any psychological work and then you get cancer, well, that's a long reach. It happened to my father. He never has a thing wrong with him his whole life, then he got Pancreatic cancer at 71 and suddenly saw his mortality. Taking him to chemo I was trying to help him through this but the look on his face told me it was too late. I would have liked for him to have one beautiful experience.

[3] - All things are just appearances. That is the only lesson one should learn who is "normal" taking LSD. I have said those same things in manic states as my friends would attest to, and I still have those experiences. You know, after a while, they are just normal like everything else. The first time I lived in Hawaii I was amazed. Then after a few years it was just like any other place.

> I never understood why people would want to take drugs to see the shit and live the suffering I have all my life but that's where we are...

Well, it sounds like you're having a bad time in your life with all of those things, and as a drug user myself, that's not the goal with my usage, and neither the effects it has on me.

Yes, I can see how a bit of this would help someone not as sensitive to trace amines as I am. I am in no way ADHD and when I was fist seeing a doc for my mental illness they thought I was an prescribe me methamphetamines which threw me into a horrific manic state.

It seems like the whole world need to get "up" and I feel like I am the only one trying to get "down". =/

Anyway, vodka is the greatest drug for me, as is klonopin. Klonopin can take me right out of my schizoaffective states. But I eat low protein, only seafood and take a bunch of zinc which all seems to help.

I wonder, if people do well on these trace amines, what is the blockage in the genetics? Not enough B6 to make the trace amines I wonder? Too much zinc?

> It seems like the whole world need to get "up" and I feel like I am the only one trying to get "down". =/

Quoting the novel that was mentioned elsewhere in this thread (and the title of the article seems to be named after too):

> We had two bags of grass, seventy-five pellets of mescaline, five sheets of high powered blotter acid, a salt shaker half full of cocaine, and a whole galaxy of multi-colored uppers, downers, screamers, laughers... and also a quart of tequila, a quart of rum, a case of Budweiser, a pint of raw ether and two dozen amyls

Not all drugs are for "getting up" or even "getting down", there is a whole spectrum of effects you can feel by different drugs (or combination of drugs even).

There are such a wide variety of effects when it comes to psychoactive substances, that's one of the most fascinating things to me about drugs.

There's far more to the toolbox than "get up and go fast"

Sounds like you have some malfunctioning enzymes somewhere. Genetic testing (through a reputable medical provider, not 23andme) may provide some interesting results

Yes, I have two runs from 23 and me one of the version four chip in one of the version five chip. I’m also waiting for my full genome that should be coming in about 5 to 6 weeks. I’m well aware of my genetics and how they helped cause my mood disorder and my various sensitivities. I spent the last 12 years teaching myself genetics and nutritional genetics as well as neuropsychology so I could figure out what was happening to my family.

Turns out we have Sami heritage we never knew we had which I think is part of the disconnect.

Based on what you've said about amines - I suspect you don't eat potatoes or tomatoes, right?

There was a recent discussion here: https://news.ycombinator.com/item?id=29131983

I seem to have a very mild version of the same thing, but I can have one of the 'dangerous' types of amine rich food every so often.

Anyway, I commend your engineers approach and working out what is good for you.

Every so often is fine for me now as well but it is a crap shoot that sometime I regret. But now since I know what it is it does not bother me as much.

If you are having trouble with amines you should think about trying high dose riboflavin. Riboflavin is the raw material for the enzyme (Monoamine Oxidase (MAOA and MAOB)) which metabolize all the amines. COMT does as well and magnesium and SAMe will help assist off that is your slow enzyme.

Before I replenished my riboflavin I could not eat even lower amine foods. Riboflavin was my cure but then it started making me depressed which is what one would expect.

Do you get migraines?

Curious that you should mention it. Yes I do get migraines, brought on by chocolate! I thought it was related to histamine. I used to think it was a tooth/dental hygeine issue but the migraine onset was way too fast for that.

Is that a sign/marker of something? If so, where did you find that out?

I eat salmon and steak semi regularly in order to avoid feeling terrible, b vitamin issues there I assume. Huge amounts of spinach for similar reasons.

The link between high serotonin and some forms of migraines is well established.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117050/

It either means your re making too much, cannot metabolize it, or you are too sensitive to serotonin.

High does riboflavin has also been shown over and over to prevent some types of migraines. It will not cure one if you take it when you get it, but curing a functional deficiency looks like it would prevent them. It takes a while for the riboflavin to turn into FAD, the cofactor for MAOA.

https://pubmed.ncbi.nlm.nih.gov/15257686/

The Phenylethylamine in chocolate stimulates the release of serotonin. https://pubmed.ncbi.nlm.nih.gov/17105921/

Speaking of histamine, most people do not know that mast cells, when they degranulate, not only release a ton of histamine, but also a lot of serotonin.

Thanks for the tips! I had not read that about serotonin release.

I'll add riboflavin to the list of things to play around with, along with levomefolic acid as recommended by the author of this comment here, who also mentioned serotonin: https://news.ycombinator.com/item?id=27990331

Might try this cyproheptadine/periactin too.

I have never heard 5MTHF called levomefolic acid before. What is interesting abiut 5MTHF is that the enzyme MTHFR which creates it from folate needs riboflavin (FAD) as well.

https://www.uniprot.org/uniprot/P42898

So riboflavin will solve both of these issues.

Would you be open to hearing out some ailments my partner has been dealing with that I feel you may have some insight on, or at least potentially shove me in the right starting direction? (prefer to do so in private communication, if so)

Sure. I sent you an email.

5HT2A mediated visual changes are different than dopamine induced hallucinations and delusions. The former are mostly recognized as being fake to the person experiencing them, and the latter are hard to impossible to discern from reality. Psychotic delusions and hallucinations are thought to be the result of problems with dopaminergic neurons, and 5HT2A exists on serotonergic neurons. Psychedelic PEAs work on serotonergic neurons mostly to produce their hallucinatory effects.

I would say that my experiences have always been on the psychedelic bent. I used to “see around” objects and peoples faces would change on TV when I was a kid.

HTR2A is a big one for me. I have the homozygous minor alleles in rs594242 and rs582385 both having been studied and linked to mood outcomes.

But the other key factor is glutamate which leads to the ego dissolution. This could be from my GRiN2B receptors. (NMDA) where I have several very low frequency polymorphisms.

It’s speaking of serotonin my TAAR6 gene is so whacked. And they found it in my set lease it led to hire serotonin levels in the brain.

I’ve only had one or two times where I had hallucinations and not visions. But I know I have dopamine issues as well because I just can’t break down the amino acids that help make all the catecholamines.

This is a good example how how very different people's biochemistry can be, resulting in massively different perception and effects of exogenous compounds. While these compounds don't agree at all with you, there are many of us who find these drugs highly useful.

I hope you can find relief some way, mental illnesses are no fun to deal with.

Yes this is true. I think knowing your genetics would go a long way knowing which drugs might help you understand the pathway to stability.

I am pretty good now, I’m disabled so I don’t have to work which was one of my hardest challenges. But I’m still so reactive to my environment that it’s just a hassle most times and I have to be careful. I will say this without a tinfoil hat on my head that I know electromagnetic radiation from household wiring and now I’m finding from Wi-Fi and smart phones are a trigger for me.

New York is fine for a visit but I'd never want to live there.

My whole life has been "Escape from New York". :)

> I am low in BH4 which limits my ability to metabolize amino acids down the common pathway and thinks like phenylalanine get metabolized dow the alternative pathways creating PEA and Tyramine. But also I have the mental illness associated changes in TAAR1 and VMAT1 and VMAT2. (I have schizoaffective Bipolar Disorder.)

this is an amazing amount of self knowledge about these topics - i'm sure some came from introspection, but for the rest - how did you find these things out or are you in the field?

seems like useful knowledge for people to have, aside from problems with over self diagnosis of course

20 years ago my life finally fell apart from my mood disorder that’s heavily genetic in my family on my mother side. So while on disability after leaving my job as a network engineer I decided to go full in and try to find out what part of our genetics was causing this problem.

I had the benefit of living next to a large research hospital which I stayed in three or four times during some of my episodes. But once the Internet really came around my learning grew exponentially.

I have the added benefit of probably having aspergers as well. I also perform countless experiments on myself using different combinations of supplements in diet. Each failure let me to great information about what was going on. Now I’m at a place where I only need klonopin on occasion. This is coming from being on four different medication‘s at once.

And thanks.

These symptoms can also he a manifestation of histamine intolerance. If your enzymes that break down histamines (diamine oxidase - DAO or histamine methyltransferase - HMT) are faulty it will be a problem.

High histamines give me the opposite of the effect of taking anti-histamines, which normally make you drowsy.

You would be amazed how many foods are high in histamines. Basically anything that is really flavoursome. And many additives either inhibit histamine breakdown or promote release from the mast cells.

Not to mention MCAS mast cell activation syndrome.

Yes histamine, but I need to correct some of what you said. It is common people think diamine oxidase break down histamine because the Amiloride-sensitive amine oxidase (AOC1) used to be called DAO in the genetic research.

https://www.uniprot.org/uniprot/P19801

D-amino-acid oxidase (DAO) is different. https://www.uniprot.org/uniprot/P14920

And the other gene is HNMT (Histamine N-methyltransferase).

I have never had histamine issues, but just to not that most ant-psychotics work on the H1 receptor and they never worked for me.

How did you learn you're low in BH4 ?

I begged my doctor for a serum amino acid test. And the pattern Of high amino acids I had on a normal protein diet were trademark low BH4.

All of these were high. Arganine, tyrosine and phenylalanine. And my tryptophan was normal.

All of my branched-chain amino acids were high as well telling me I had a B6 deficiency.

Chocolate also has caffeine, which may be what’s keeping you up.

Yes, maybe the caffeine, theobromine and PEA all together effect me. But I know my phenylalanine is high from blood tests.

“ I never understood why people would want to take drugs to see the shit and live the suffering I have all my life but that's where we are...”

Maybe you just have no idea what you’re talking about and these drugs don’t produce an experience that resembles “schizoaffective Bipolar Disorder” in most people.

Well I was more talking about the schizoaffective part. Ego dissolution is a large part of a lot of peoples schizo affective/schizophrenic experiences.

But I remember growing up when my friend started taking psychedelics and told me about their experiences, well that’s when I knew there was really something different about me because I never took the drugs yet their experiences were familiar.

I just don’t think we’re all supposed to see the world in the same way. I don’t mind my schizo affective side as much as I do my bipolar side. The bipolar part is much more disruptive in my life. But I think there’s a place for people who don’t see these things. They are valuable to me. You are valuable to me just as you are. Maybe it’s not that you need to take his medication’s but to listen to people like me when I say the ego is an illusion.

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