Phenethylamines I have feared and loathed (2020)
nikobidin.com
nikobidin.com
https://en.m.wikipedia.org/wiki/Fear_and_Loathing_in_Las_Veg...
Edit: actually scratch that, I have no idea (obviously) what the author had in mind, and could be either.
The first, that occurs in a Cadillac convertible bombing toward Las Vegas at 90 mph, has the author seeing big black, bat-like things swooping around the car, and choosing not to mention them to his companion: "He'd see them soon enough, poor bastard."
The second is in the lounge of a hotel on the Strip, when the author suddenly realizes that everyone else in the room is a vicious, bloodthirsty reptile, and the whole floor is a puddle of shed blood.
Edit: I’ll add that “snaps back to reality” happens if you’re lucky and somehow stay in control
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...
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.
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?
Turns out we have Sami heritage we never knew we had which I think is part of the disconnect.
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.
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?
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.
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.
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.
https://www.uniprot.org/uniprot/P42898
So riboflavin will solve both of these issues.
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's far more to the toolbox than "get up and go fast"
I hope you can find relief some way, mental illnesses are no fun to deal with.
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.
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 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
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.
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] - 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.
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.
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.
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.
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.
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.
A visual, not too uncomfortable cousin of LSD. Except the risk profile was completely different.
25i, 25c, 25b, 25d nBome's. The "fake acid" that your high school administration actually had a reason to fret about.
Ironically, xanax is what actually should had had the attention. Maybe the high school administration were taking/selling too much Xanax to see the issue.
People who take Amphetamines because they want more energy end up tired, etc.
If you're doing that, what you actually need is 8+ hours sleep, proper sunlight and exercise, a sleep apnea check, and then maybe buy adrafinil off the internet (where legal).
So I just wanna kind of correct what you said, Xanax is for people who think too much and psychedelics are for people who think too little.
Benzos are bottom of the barrel drugs as far as I'm concerned.
The fact that they are still regularly prescribed by some doctors to the elderly (for no other good reason than to get them off their face) is borderline criminal.
They are horribly addictive and withdrawal can kill, as can OD and mixing with anything else has potential to kill, so clearly they aren’t without issues. But when used in a measured way I found them to be lovely.
I’ve never taken Xanax though, it’s a lot longer lasting than the stuff I tried.
I also tried etizolam, which has a half-life around 3.5 hours, but its active metabolite has a half-life around 8, so the effect tended to hang around a bit into the next day. Apparently flutazolam also has an active metabolite that lives longer ... but it never seemed apparent.
At the time both of these were freely and legally importable into the UK where I lived. This is no longer the case, and that's probably for the best - RC benzo use was getting to epidemic levels.
(incidentally, reading up on this, I have realised that xanax is not a lot longer lasting as I initially said, it's actually pretty short acting for a benzodiazepine, around 1.5-2x as long as flutazolam AFAICT)
None the less, interesting to see this list on HN, and read about some new compounds I haven't heard about before (hello 25B-NBOMe).
One summer when 25i first hit the scene SWIM was taking 1000 to 5000 microgram doses weekly until one week SWIM dosed 1000 micrograms (pre dipped blotter) and the short version of the story is SWIM woke up in the hospital and was being monitored to prevent kidney failure due to elevated proteins in SWIM's blood.
Similar events which were all preceded by psychotic breaks with reality happened to quite a few of SWIM's friend group if you want some anecdata to add there.
It's scary stuff whose unpredictability means I wouldn't recommend touching it with a 10 foot pole.
There are other dangerous phenethylamines, of course. Bromo-DragonFLY caused vasoconstriction which resulted in amputations or strokes in overdose, many others including the 2C-Ts are MAOIs. And even LSD has catastrophic effects when taken with lithium. But there's something about the NBOMes, maybe off-target effects, that makes them terrifying.
...which is a shame because having a new backbone to play with would be super fun. we have phenethylamines and tryptamines and ergolides, but there's only so much you can tweak them. hopefully - eventually - Shulgin's style of gonzo pharmacology will be allowed again, and someone will discover more magic keys.
Source: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5552826/
They reproduced it in zebrafish, apparently. They suggest using 25B as an actual research chemical to study serotonin-induced rhabdo in lab animals shudder.
From what I could tell back then, 'I' was the most likely to cause problems. B and C seemed to be relatively well tolerated, though not trouble-free.
subjective effects have been described as “like being dragged to hell and back again. Many times. It is the most evil [thing] I’ve ever tried. It lasted an eternity.” Oh and it lasts up to 3 days. No gracias.
If you feel fine, you wait several days and try a bigger dose, then see if you feel any effects. Stop when it becomes unpleasant or unwise.
This is not safe. There is no safe way to ingest dozens of unknown chemicals. Somehow, chemists like Shulgin show that it's possible to test all those compounds on yourself and still live a long healthy life. Still, I would not recommend tempting fate.
If you absolutely must experiment, this method is a good for hopefully avoiding short-term adverse effects, but not long-term ones.
Much safer is to stick to substances that have a long history of safe human use.
> Much safer is to stick to substances that have a long history of safe human use.
Yeah, so much is clear, but saying "stick to the classic ones" when one brings up experimentation with new ones doesn't bring much new to the table. Much better to provide education up front on how to dosage new drugs (not just new to the world, but new to your body too) for the ones who do want to exist in that space.
That is despite a (smaller) subset of them being careful and methodical with dosage.
Personally, as a very squeamish person, I'm more than happy to stick with the tried and true, and in desperately boring moderate amounts :)
Yes this is aggressive, and yes I'm quite angry about how these laws have held back scientific progress.
Say what you will about the recreational drugs of the 20th century, their long-term effects are well understood.
> Here Gibson quite clearly took artistic license with his chemistry, and I don’t necessarily blame him. Beta-phenethylamine refers to an extremely broad class of compounds (of which amphetamines are the best-known members), similar to how “tropane alkaloids” does.
http://www.chemistry-blog.com/2018/04/16/the-chemistry-of-wi...
2C-B is a fun one. Good times have been had there.
LSD is a different ballgame from the 2C family IMO, its difficult to compare. From my experience (again this is quite subjective) the visuals from LSD weren't as "thick" and deeply colorful. They had a sort of whispyness to them and (usually) a much deeper headspace
This is what I remember about 2CB. It looked like the Matrix effect to me but in translucent rainbow colors.
Purity and accurate dosage is a function of your vendor. Buying 2C-B pills will be more dangerous, they are notoriously underdosed and should ideally be sent to a lab first, but at the very least spot-checked with a reagent test kit.
Duration is a subjective preference, I feel. LSD is nice, I like it very much, but I can understand than 12 hours uninterrupted is not something everyone can allocate in their schedule.
I stick to low dosages, partly to avoid nausea and partly because I like to be somewhat cautious with this delicate biological machinery I don't understand.
For me it's also something I can take a small dose of occasionally when I have a big night out, if I'd like to sleep early, or if I'd like more stimulation and less headspace.
LSD I use for long introspective trips, physically by myself so that I can tune in and out of online social interactions depending on how I feel.
I feel like 2C-B is a nice option to have for different settings. Since I don't very much experience the downsides it's worth it for me, but I can definitely acknowledge the downsides =)
Zofran works for my friend, zofran. Whether it’s specific serotonin blocking effects that fixes the nausea has +/- psych experience is unknown.
(Supposedly it can contribute to serotonin syndrome, but I don’t understand the mechanism. Seems theoretical, but don’t say I didn’t warn you).
It is mentioned in the article:
"these and other reasons make me suspect that even 'safer' phenethylamines like 2C-B won't be getting FDA approval anytime soon."
Before Shulgin published Phenethylamines I Have Known and Loved and Tryptamines I have Known and Loved, Donald Cooper of the Drug Enforcement Administration wrote this prescient 1988 document titled "Future Synthetic Drugs of Abuse":
https://erowid.org/library/books_online/future_synthetic/fut...
It's like looking into the 2000s from a vantage point of the 1980s. What was really necessary for wild and woolly synthetic drugs to take off was digital infrastructure. That is, tools for collaborative and secret discussion, research tools [2], and (more recently) darknets.
The thing that finally made me stop following the scene was that I liked the how-to hacking aspect of the chemistry. There were tons of threads about how to make equipment, source chemicals from unexpected places, and synthesize the critical intermediates that were on watch-lists so they were difficult/inadvisable to buy commercially.
The last forum I followed closely ("Blacklight") ended up with members just theorizing about interesting points in chemical space and then outsourcing the manufacturing to commercial contract labs, mostly in China [3]. The only actual chemistry that would be done outside China was instrumental analysis (to confirm composition/purity of products). And the scene became secretive and scheming about people spotting chemicals that were subjectively good enough to become popular and commercializing them in Europe before the law caught up. (It's globalization in miniature! Keep marketing and management domestic, but offshore the low margin manufacturing work.)
The Hive wasn't like that. Most of the chemicals the members wanted to make were old stalwarts -- amphetamine, methamphetamine, MDA, and MDMA were the most popular. All the close analogs were illegal already so members were united in finding ways to hack around the restrictions. Nobody expected to hack around the law itself, i.e. to escape without consequences if the law caught them with the output of their clandestine labs. All questions that indicated someone was trying to scale up to major commercial manufacturing would get banned anyway. So users were generally collaborative rather than competitive. Everyone would pitch in on e.g. trying to figure out how to remove pill binders from OTC decongestants so that the purified pseudoephedrine was suited for downstream transformation to methamphetamine. Even people who wanted to manufacture less popular or more obscure compounds really wanted to do it in their own garage -- not in a contract lab.
[1] https://web.archive.org/web/20040103031950/http://the-hive.w...
[2] Back when The Hive was active, there were huge ongoing request threads for people trying to source research papers. Other members would have to go to a library, photocopy articles from the stacks, and upload scans. It was a huge breakthrough when the American Chemical Society actually scanned its complete print run and made those available to subscribers online; then members could just download requested papers from their company's/university's account. Then sci-hub solved even the part where someone has to manually request a paper.
[3] This preceded the rise of imported fentanyl by several years. In fact I wouldn't be surprised if small time (but technically advanced) Western drug dealers actually kickstarted the trend of getting potent opioids manufactured in China.
As someone fascinated by chemistry since childhood, I was in digital heaven. I was far too risk averse to consider making controlled substances myself, but I loved participating in the publication-sourcing and equipment discussion.
[2] https://www.erowid.org/psychoactives/psychoactives.shtml
https://www.sciencemadness.org/whisper/viewthread.php?tid=63...
https://the-hive.archive.erowid.org/forum/forums.pl
You can read it again now even though none of us can go back in time again.
This goes deeper. For example, the stimulant-antidepressant herbal brew known as coffee is a staple at offices, but someone taking caffeine pills is seen as a drug addict, even though they are the one who knows what they are taking and how much.
Similarly, tobacco smoking, even if disliked, is more acceptable than vaporizing nicotine liquid, even though vapers know what they are taking (pure nicotine) and how much - commercial tobacco smoke contains hundreds of psychoactive substances in addition to nicotine.
BUT, for some reason, natural cannabis is looked down upon, and extracts and synthetic compounds are somehow considered more a-okay.
https://psychonautwiki.org/wiki/DOB
24 hour nightmare trip, felt like I'd been awake being haunted for weeks.
I know someone that snorted some 25i-NBOME thinking it was something else and started seizing, and nearly died. In hospital for 2 weeks. Kidneys almost didn't make it.
As somebody that experimented heavily with psychedelics when I was much younger, my opinion is that the 2C-B/E/I group have definite possible therapeutic value, and the main thing causing stagnation is the ridiculous hippy mindset that it’s ~synthetic~ and therefore bad. It’s ridiculous.
Over the past few years it’s been interesting watching polite society “discovering” psychedelics. I really can’t wait for these people to find the therapeutic value of smoked/IV DMT, especially considering that it’s WAY safer than ayahuasca.
I would love to see a study on the possible therapeutic value of dextromethorphan, but as far as I’ve seen it’s not really on the radar. I know it seems weird, but from subjective experience I found it to be very helpful a few times as a teenager. I used to jokingly call it “therapy in a bottle.” It’s a real shame that most DXM-containing products nowadays in the US come mixed with other compounds that make it dangerous to take at a recreational/therapeutic dose.
I agree with GP. If ketamine works for depression, there's no reason to think similar effects wouldn't occur with DXM. I've always found the 'next day' glow to be quite nice.
From what I understand, ketamine's rapid antidepressant effect was once thought to have been mediated by NMDA antagonism. However, countless NMDA antagonists have been studied for depression, and their efficacy was nowhere near the S-enantiomer of ketamine, suggesting that NDMA antagonism alone isn't responsible for the full effect.
DXM acts as a dirty serotonin reputake inhibitor before it's metabolized into DXO, which is actually an NDMA antagonist like ketamine.
By combining DXM with bupropion, the bupropion prevents the DXM from rapidly metabolizing into DXO through enzyme inhibition, leaving more SSRI-like DXM in the blood to affect the brain. Bupropion itself is a potent inhibitor of enzymes that metabolize many pharmaceuticals.
So the idea behind combining DXM+bupropion to treat depression doesn't really come from the same mechanism of action that esketamine has. It's more about the SSRI-like properties DXM has in the body as long as it isn't metabolized into DXO.
Also, combining two medications that are off-patent for a new treatment means that you can patent the new combination as if it's a new drug. I suspect that's why it's being investigated. Both DXM and bupropion have pretty good safety profiles, they're cheap to manufacture, and the combination can be patented.
Interestingly, there's a small trial with just DMX (300mg - aka first/second plateau) to determine safety: https://clinicaltrials.gov/ct2/show/NCT04226352 The bupropion seems to be only useful for slowing the DXM->DXO to allow for lower doses. A full on 'robo-trip' may actually work as well as a full on ketamine trip.
DMX is really a crappy drug with a half-life that is too long for frequent administration.
I’m not sure I’ve ever experienced the afterglow in the way many people describe it. Next day I would just feel kinda drowsy, and a bit muted and dumbed down.