For anyone who is confused by the title: this is a variation of the book name "Phenethylamines I Have Known and Loved", published by a scientist couple in 1991.
Probably referring to the book/novel rather than the movie, as the book is autobiographical in nature and a fascinating read, while the movie is more pure entertainment.
Edit: actually scratch that, I have no idea (obviously) what the author had in mind, and could be either.
The book had two of the most enduring images in all of modern literature.
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.
I wouldn't call the movie pure entertainement, quite the opposite. It can be seen as that, but there are a few scenes that really stays with you if you've ever fooled around with drugs. The most obvious ones are when the narrator talks about San Francisco in the 60's, and when he talks about the "fallacy of acid culture" near the end. There's also something to be said about the "white rabbit" scene, though it's hard to put into words.
The scene in the casino waiting room/bar where things start to drift from normal to absolutely crazy (reptiles and all the blood) and then snaps back to reality is a pretty accurate depiction of LSD
Edit: I’ll add that “snaps back to reality” happens if you’re lucky and somehow stay in control
There is, its the first half of PIHKaL. It about the experiences and the society, not the chemistry. The second half of the book is the chemistry. Often in free dls they dont include the first half.
The first part of PiHKAL, written by Ann Shulgin, is also completely non-technical and is a spellbinding story. Highly recommended for anyone interested in the subject matter of the book, whether they know chemistry or not.
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...
[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).
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.
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.
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.
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.
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
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.
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)
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.
> 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.
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.
“ 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.
25b was a very commonly found compound in 2012-2014 gen 1 Silk Road era.
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.
Xanax is for people who don't want to think, psychedelics are for people who feel they can't think enough. Accidentally, (too much) Xanax turns people into zombies who can't think while (too much) psychedelics turns people into aliens that talk a different language than everyone else.
Amphetamines at therapeutic doses are safe and neuroprotective (and even prevent substance abuse), but if you're abusing them "for energy" that's not a therapeutic dose.
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).
Benzos bring me to a place where all of you people live. I take klonopin as needed because I think way way way way way too much. I know glutamate plays a large role in my schizoaffective disorder and I can bring me out of an involuntary trip and a half an hour.
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.
And benzodiapeines withdrawal is insanely painful to overcome.
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.
I like them. They make me feel beautifully relaxed and allow me to get a wonderful night’s sleep. I used to take a dose once every week or two, and I would always wake up feeling wonderful.
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.
Really? I'd be interested in knowing what it was you had. As far as I understand, xanax is one of the quickest acting benzos on the market. With something like valium being the traditional interpretation of 'long acting'.
https://en.wikipedia.org/wiki/Flutazolam, from Japan. It has an elimination half-life of about 3.5 hours compared to 11-16 for xanax. Valium is around 50 hours IIRC.
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)
Agreed. The "good" feeling was so terrifying, so alienatingly remote from any sanely-achieved accomplishment/reward that I have had a hard time ever taking it again, unless to cancel the effects of psychedlics.
FYI, I've taken 10mg Xanax during a trip that wasn't going well and it did literally nothing. Normally, 0.5mg would put me to sleep. Seroquel (Quetiapine), on the other hand, does work if you want an escape hatch and don't mind being sedated.
The author mentions that 2C-P has "notable physical discomfort" and I can attest to that, although I didn't have effects for as long as stated (my trip was more around 7-8 hours, author states "up to 20 hours", and my onset was also faster) it had a significant discomfort, especially when compared to 2C-B which induces a loud, unstoppable euphoria. It wasn't as much of a physical discomfort but a mental one. Eventually what calmed me down from the 2C-P was watching a newly released movie I never really bothered paying attention to before, Avatar.
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).
I'd stay far away from any compound in the 25x-NBOMe series. The risk of life threatening episodes are real and understated in TFA with erratic responses to even low doses in experienced and first time users.
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.
The whole NBOMe/NBOH series are notorious for that. Some people have incredible visuals and a gentle time, others go psychotic or randomly die.
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.
Can't edit my post anymore, but researched and (some of?) the NBOMe toxicity appears to be from rhabdomyolysis (your muscles break down, releasing proteins that cause your kidneys to fail.)
They reproduced it in zebrafish, apparently. They suggest using 25B as an actual research chemical to study serotonin-induced rhabdo in lab animals shudder.
It's been a long time since I heard anyone say SWIM. I thought we all recognized that it wouldn't hold in a legal context and was thus unnecessary. I dont know if it was true but I distinctly remember that conversation happening at least a couple times in a couple places and the use of SWIM fading out after.
I can't imagine trying unknown drugs on myself. That's so risky. But people did it and found out the hard way like with Bromo-DragonFLY:
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.
The way to test these things is by starting with an alergy test, a dose low enough that it definitely won't have any effect, and also definitely will not kill you.
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.
"The way to test these things is by starting with an alergy test, a dose low enough that it definitely won't have any effect, and also definitely will not kill you. 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."
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.
Absolutely. If you're looking for examples of things going wrong, the researchchemicals forum unfortunately has more than a few cases of people showing symptoms of serious nerve damage after experimenting with NPS ('novel psychoactive substances') stimulants ordered from RC vendors.
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 :)
It's sad that the war on drugs is just pushing recreational drug users (often unknowingly) to more-readily synthesized chemicals with worse safety profiles, thereby increasing the net harm to society. It really puts the lie to the idea that harm reduction is part of the agenda in most western countries.
Say what you will about the recreational drugs of the 20th century, their long-term effects are well understood.
Long-term effects tends to come from prolonged use or very high amounts, not from doing smaller tests.
> 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.
I think the main problem with bromo-dragonfly is that the active dose is somewhere around 200 micrograms, around 50-100 times more potent than what they were expecting (2cb-fly). In fact there’s very little other than lysergamides and some opioids that’s active at that level. I guess some sort of volumetric dilution might have helped, otherwise I t’s actually pretty difficult to dose that low.
The fatalities with bromo-dragonfly where due to a mix-up on the distribution end, not only because of the inherent danger of the drugs. In fact, the local distributor (known as Haupt RC) in the bromo-dragonfly 2c-b-fly mix-up incident, died himself.
Of course, self-titrating new chemicals is not without risk, but Shulgin style careful titrating usually prevents incidents comparable to the bromo-dragonfly one and various other ones (such as unreliable dosing of NBOMe derivatives etc).
Its also customary to start at extremely low doses and slowly work your way up until activity is noticed. Iirc this is all detailed in pihkal/tihkal along with explanations of the Shulgin scale
These folks are also very experienced chemists who can model the structures of the chemicals they are synthesizing and make reasonable guesses about their effects.
Not sure I would want to put that kind of information in the cloud where a paper trail could be potentially used in court to argue impairment in ANY kind of dispute.
This is not subject I know anything about, but I just realized that "betaphenethylamine" is (I think) the drug Case is taking in Neuromancer because normal drugs can't get him high due to a modification in his pancreas. Maybe not entirely accurate vs this list, but William Gibson continues to amaze me with little details like that.
A chemist's blog took a look at the drugs mentioned in Neuromancer. He speculates about the nature of the surgery to put in a new pancreas and "liver plugs".
> 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.
Seemed overrated to me. Maybe I got the dose wrong but the purity can be so inconsistent that everyone's going to have a different experience. I'd much rather take some classic LSD, you know what you're in for and it doesn't end disappointingly early like 2C-B.
I'm surprised, because you don't often hear that particular criticism of 2C-B.
Mostly, people complain about nausea, or the fact that it burns very painfully when people insuflate it
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.
Yep, I spared the details regarding nausea but the contents of my stomach were definitely emptied once or twice. As far as I remember it wasn't anything special and the additional side effects and risk you describe make it just not worth it in my opinion.
That's fair enough. I did hear it repeated a lot that 2C-B's dosage curve seems to be particularly steep and non-linear. I don't know that it's been studied very scientifically, but reportedly the difference between 40 and 50mg is much bigger than the difference between 20 and 30.
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 =)
Snort it (hurts really bad for 5-10 minutes, afterwards okay, redosing takes its toll though...) can help with the nausea. I make a solution so that I can use a nose spray to dispense about 2-5mg per pump. Then I can redose every 15 minutes until I get to a dosage I enjoy.
2C-B has a very "surface level" high compared to LSD, which can absolutely make your mind go into itself, 2C-B doesn't take itself as serious. 2C-B can be fun even in larger groups where you don't know people too well, and it's mostly just visual gags and euphoria that happen. LSD on the other hand requires a personal connection to everyone in the group already, triggers deep introspection and is not nearly as visual as 2C-B, and euphoria only happens when it would happen in real-life, but LSD can easily make you go down the other road.
2C-B was enjoyable but seriously lacks introspection from my experience. It felt like "psychedelic-lite" where the visual effects are quite pronounced... but that's about it
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
A little more than a decade ago I ordered a bag of 2C-I, shipped to me via snail mail from China. One of the most enjoyable psychedelics I've ever tried. At the time 2C-B was already harder to get and I was a little bummed out I had to settle for something less known.
i probably ordered some about the same time as you. 2cb had become impossible to get. so i got 500mg of 2c-i. was my sunday trip for many a sundays. very low key and relaxed trips for me
This post was a real trip down memory lane, back to the days of the Hive [1].
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":
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.
[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.
Rhodium was the university's library. The Hive was the university's classrooms. Or something like that. I think I came across Hyperreal [1] first, by way of my interest in electronic music, which linked to Erowid [2], which led me to Rhodium and the Hive.
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.
> On a cultural level, we’ve decided that if a therapy is run with a shaman using a completely chemically-uninterpretable drug cocktail: totally a-okay. But if it’s run with a synthetic pure compound of known quantity: immediate banishment.
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.
So for others wanting to go down the psychedelic road I recommend reading a lot of psychonautwiki.org and picking a lighter experience and working your way up, for sourcing the psychedelics it's quite painful and requires reading up on reviews for sketchy sites that accept payments by non-refundable means and have sometimes not filled orders for customers.
The Controlled Substances Act needs a carve out for substances so strange, obscure and nerdy they would never achieve mainstream popularity or public health effects, but that would require drug policy having some character of consistency and reasonability. A cruel joke where you can only laugh to keep from crying!
Won't happen because the CSA is policy to create make-work jobs for law enforcement and the justice system. It also ensures that there's a steady stream of the incarcerated to keep prisons occupied and prison labor programs populated.
Most of these are extremely toxic at overdose amounts, as opposed to tryptamines which generally just give a stronger trip.
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.
I’m glad to hear people discussing this! I love how most of the hippies that love “natural psychedelics” have a loophole for LSD. Just because a drug has a precursor found in nature doesn’t make the drug itself natural.
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.
See also, Nuedexta, which is used to treat pseudobulbar affect (PBA.)
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.
> 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.
I don't think the SSRI effects are the primary goal. The appeal of esketamine is its rapid effect, the same thing being sought with DXM+bupropion (AXS-05). Studies with naltrexone and ketamine reduced the antidepressive effect, so maybe the mu opioid or sigma-1 are important. (https://www.cambridge.org/core/journals/cns-spectrums/articl...)
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.
I think there's an argument to be made that a working opioid system is central to the anti-depressant effect of any anti-depressant? I actually tried naltrexone for a condition related to depression and it made me feel much worse and unable to feel much pleasure in anything.
DMX is really a crappy drug with a half-life that is too long for frequent administration.
> I've always found the 'next day' glow to be quite nice.
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.
I would likely agree with all the conclusions here besides one of them. 2C-P is a fascinating compound and while it may be difficult to administer orally in therapy, there may be other viable routes. The subjective headspace of extreme introspection induced by this compound is absolutely incredible and will make you seriously examine how you feel about your self.
https://en.wikipedia.org/wiki/PiHKAL