This is fantastic. Anyone know of an article that delves into this more? Assuming it's true, I'm surprised it isn't more widely known.

http://motherboard.vice.com/blog/the-first-thing-to-be-bough...

Apparently the anecdote is from this book:

http://www.amazon.co.uk/What-Dormouse-Said-Counterculture-Pe...

People are taking a big risk with some of these designer drugs. Just because a drug looks like an illegal drug doesn't mean a dam thing. Sometimes a simple modification of a molecule (methyl changed to ethyl or a hydrogen replaced by a bromine) can completely change the safety profile of a drug.

We've found that legalizing marijuana has so far been helpful. I just hope it's not the last step.

That doesn't make sense to me.

Also, as MarkPNeyer said, a lot of drug users are rather depressed.

Few are going to huff gasoline if cocaine is available on a liquor store shelf.

The same thing is starting to happen to the fast-food companies like Mcdonalds. They are starting to take the blame for a person's free choice to consume their unhealthy food.

How can a company (or government) possible allow the legalized consumption of something like Cocaine/heroin/Meth? Will there be tort reform so a company can't be sued for deaths or addiction?

Until we have a little more personal responsibility, I don't think illegal drugs should be legalized. It's even apparent in your comment:

"And these shenanigans, too, would be entirely unnecessary if known drugs were legal and regulated, and people could take controlled risks instead of playing Russian roulette with newly synthesized drugs."

It's your personal choice to play roulette with drugs. They aren't required to live and the ones you are talking about have almost no health benefits (we aren't talking about weed here). Yet, you someone blame the government for forcing a person to make this choice. Complete and utter bullshit.

We see big companies frequently taking part in tax avoidance by going overseas. Should we also blame the US government for having taxes that are too high? It's the same logic you are using.

No matter if you forbid it or not people will want to take drugs. The government can either forbid it and cause the raging war on drugs that claims lives, leads to the development of underground mafia organizations, or choose to regulate it and make profit from it while keeping the prices reasonable and under tight control in terms of quality and supply.

Your tax money going to the war on drugs has been proven to be completely useless so far, so I can see the benefit of the other point of view.

All the big cases I'm aware of are the ones stemming from their decades-long lies that smoking was not a health risk.

The government is the organisation that chooses to regulate the behaviour of it's citizens. Why should the citizen need to make a case for need? Shouldn't it be the other way round?

Yes, the frequency of tax avoidance is proportional to tax rates.

This is a common argument in finance and economics articles.

Likewise, putting myself in this driver's seat, an overdose on my part is my own fault: If I chose to gamble in such a fashion, it does not seem fair that medical staff should have to labor over rescuing me. I made a decision, it only seems fair that I abide by the consequences. Assuming I had not previously entered into a contractual agreement that was pre-financed, an insurance of sorts, premiums paid up, expectations laid out (DNI/DNR, etc.).

I guess the rub would be if the dosage was administered to me without my consent, or a substance included (cut in) that I did not authorize...

With the same preface, this would logically extend to some other "for your own good or the lesser financial burden on others" laws, possibly like helmet laws.

I get the overall feeling that we have short-circuited the benefits of natural selection/survival of the fittest/most able to adapt. Which probably explains my enjoyment of the Darwin Awards books...

Oh, you meant only the "bad" drugs, not the "good" drugs. Never mind.

http://www.bluelight.org/vb/threads/582708-I-like-to-draw-pi...

The degree of effort to which people will go to satisfy their curiosity is sort of astounding. There seems to be an endless array of possibilities. The thing is, people who have some understanding are always trying to direct attention to structures that won't cause grievous physical harm, stuff we understand, and so it is usually these that get popular -- there's a reason that synthetic cannabinoids have fluoropentyl chains on the indole nitrogen instead of fluorobutyl chains, and it's because the latter will tear your mitochondria to shreds (fluoroacetate). Unfortunately, as more stuff gets banned, we stray further and further from the beaten path -- methylone was pretty similar to MDMA, but we know a lot less about 6-APB, and whatever comes next will probably be even stranger. Every now and then the predictions fail and something nasty like 5-API shows up on the market and people die, and we don't know what to do about that because there will always be effects we can't predict. Even as we do our best to recommend the things we think are safer, we inevitably shuttle those off the pipeline into prohibition and rush forth to the next scary-looking arylalkylamine.

It's a mess. Most people in the harm reduction community want legalization, but none of us wants this. We actually have plenty of drugs that have a history of use and no reported deaths (mephedrone, 2C-B), but of course those got banned, anything that becomes popular gets banned, even if it appears to be safe (Al-LAD on the chopping block) and we go back into the dark again, waiting for the tide of profiteering to carve a new vista out of the world's insatiable demand for something more entertaining than football.

http://www.vice.com/read/interview-with-ketamine-chemist-704...

Those are moved into country, mixed with all kinds of chemical shit and sold as "курительные смеси" - mixes for smoking.

This fall dozens of people died from these nasty chemicals, usually in packs in one city or another. There was a law passed which makes all that stuff illegal but I'm not sure if it will pan out.

Why they proliferated so badly? I guess because the local market of [relatively] light drugs is underserved in general. For example, I happen to not have ever come in contact with weed and don't know a single person who can get some. But pretty sure there are a lot of advertisements like "курительные смеси 8 9XX XXX XX XX" mask-painted on pavements all around the city.

It doesn't surprise me that injecting a drug that has left over phosphorus triiodide or other phosphorus/iodine compounds would destroy your tissue.

If you look at desomorphine, it's just a morphine molecule without the bottom hydroxyl group and the double bond reduced.

HI will reductively deoxygenate benzyl alcohols. The oxygen removed in morphine is an allyic alcohol which is in conjugation with the aromatic ring, so it has "benzyl alcohol-like properties". HI will also reduce the double bond.

As for the reaction mechanism, I'm not sure anyone has completely figured it out. One could suggest protonation of the hydroxyl group, elimination of water to form the carbocation, addition of the iodide ion(-). Another iodide ion then attacks the iodine on the molecule, which creates I2 and leaves a benzylic anion which is protonated by HI. Here is a good mechanism diagram [1].

[1]http://www.beilstein-journals.org/bjoc/content/inline/1860-5...

I'd be super curious to see whether anyone has properly analysed what comes out of that reaction, and what those addicts are putting into their veins (aside from horrendous toxic byproducts). The reaction method makes some sense, but reactions with opiates are typically finicky, so I've always been skeptical of these reports. I'd expect desomorphine to be present, yes, but in trace amounts at best (along with morphine and other byproducts)!

I'm not sure what makes it so hard for some people to grasp the intrinsic dangers of ingesting "designer" drugs. Our physiology is complex and quirky, rendering all drugs capable of unpredictably causing serious side effects. And even if that's a rare event, in the case of barely (or not at all) studied compounds, it's still like playing pistol roulette with live rounds.

There's risk for the chemist too. While we might admire the skill to design and synthesize a novel compound, it's foolish to do so outside of a fully equipped and qualified lab to assure safety for the chemist as well as the environment. Of course, working in such a lab would no doubt imply a level of scrutiny about what the chemist is trying to do.

So obviously a designer drug is likely to be produced in conditions that don't favor purity and careful testing. It's no wonder there are tragic outcomes, but it seems human nature to try to do something "against the rules". But it's an entirely different matter when rules are the "laws" of legislatures vs. the laws of Mother Nature. She never cares what we "believe" or desire.

Designer drugs will continue to be a problem. The best we can hope for is that bad outcomes will yield here and there a clue to something useful. It's a shame, seems so often we have to learn the hard way.

I can see your line of thinking: X has risks, X should not be done, thus make X illegal and X will not be done and the risk will no longer exist.

But that's not the way the world works. Making X illegal does not prevent X being done. Instead, it creates incentives try and find people doing X and put them through the criminal system. That introduces a whole separate set of risks. And making X illegal reduces the probability that problems created by X will be treated in time. Another set of risks. Etc.

The question you should be asking is: are the risks of X greater than the risks of making X illegal?

I ride motorcycles. I have friends and family involved in scuba diving, paragliding, football, rock climbing, hell - even horse riding.

_All_ of those activities have "well known risks of serious injury or death" associated with them, and each of them I've heard recent stories of death in the extended circles of my family and friends.

I'm not sure whether the "designer drug" risk is anything like as high as some of those legal and "acceptable for your children" risks.

My approach is less "asking are the risks of X greater than the risks of making X illegal?", but closer to "Quantify the risks of X, work out which can be mitigated or reduced without needing to ban X, make sure participants are informed of the risks, and if needed ensure training/insurance/licencing is available if required".

Thirty thousand people a year are killed in motor vehicle accidents in the USA. We don't react by saying "Make cars illegal" - we manage, mitigate, reduce the risks (quite successfully, that 30k is down from 40k 10 years ago, and over 50k back in '79 and '80) - then we declare 30 thousand dead people a year an "acceptable cost" for the benefits of private car ownership.

Why aren't we able to be that rational about "designer drugs"?

Point is with motorcycles, cars, scuba, yes, even horses, the risks are more or less known and probability of various outcomes, including harm, can be reasoned about.

With drugs the estimation of probable outcomes is orders of magnitude more difficult to compute. To say it again, all drugs have numerous effects which vary greatly among recipients, and even for established agents most drug effects have received little or no study. However we do have a systematic track record of the AEs encountered, and after millions of cases we have a pretty good idea of how to use the agent safely.

Legal status notwithstanding, a drug with potent enough effects to be interesting is asymptotically guaranteed to have adverse effects in some members of the population of potential users. It means effects of a new and arcane product are no more than a total crap shoot.

Since even low frequencies of AEs may disqualify a drug as "safe", regulatory bodies require testing sufficiently large number of subjects under tightly controlled conditions to show evidence that it's safe enough to justify its proposed uses.

Without such study it is impossible to evaluate the use of an unvetted drug in the same way as riding a motorcycle. The information about benefits and risks is just not known. There is simply no basis for making a rational decision.

As a clinician and scientist questions of prohibition are largely beside the point. People will continue to do stupid things laws aside. However, laws/rules exist as a benchmark, and optimally serve as a statement of our communal ethical stance. Not that it's going to stop people who are determined to use a prohibited drug anyway, but maybe it supports restraint in some people who are "on the edge".

In respect to designer drugs, I'm very reluctant to say let's have no regulations at all, that anything goes, because logically lack of safety data leaves us to assume the risk of harm is significant. The burden of proof ought to be on the shoulders of those who assert use of the drugs is just harmless diversion.

Which is why we should legalize and regulate the drugs that we do understand. The risks of cannabis and LSD are also more or less known, and the (remarkably low) probability of harm (particularly compared with motorcycles, cars, etc) can be reasoned about.

The harm in making these well-understood substances criminal is far greater than the harm in regulating them. Indeed, as the GP points out, the harm in making the well-understood substances illegal is exacerbated by the harm from designer analogs.

As a clinician and scientist questions of prohibition are largely beside the point.

You're simply pulling the wool over your eyes if you believe that to be true. Prohibition is a causal factor in the danger of substance abuse.

Too lazy to look it up, but if I remember correctly that one of DEA chiefs was also head of some UN panel on drugs, which then enforce rules for all UN member states (read whole world maybe except North Korea). From first glance, it might make sense. But show me one career-oriented competitive guy (and being head of such an agency, you have to be at least that, and have a lot of political games skills), who would undermine his own little kingdom, and make his own subordinates lose job by declaring that some of most popular drugs shouldn't be banned. One real example - weed & hashish have thousand years of history in hindu culture (look up shiva day when almost all india is high), yet they had to ban it after they joined UN.

So, we can thank those guys for making policies that worldwide raise crime, help supporting organized crime on massive scale (brutal mexical cartels are a fine example, out of many, ie afghanistan)

It's like thinking, that in banking/trading/brokering, it's always the client's best interest that's primary drive. Well yes of course, unless the bussiness is funded mainly by operational fees. WHat do those brokers do? Make you do as many operations as possible, of course, without being too obvious :)

(*no references here :))

A new legal drug in its first iteration frequently through animal models frequently has a breakdown of 80% or more effectiveness, with the balance of the population mostly experiencing no effect and a small remaining fraction experiencing negative side-effects. The drug will then be tweaked and twisted to increase the size of the population it is effective on and drop the size of the negative side-effect population to as close to zero as possible.

This is a hugely expensive process. It is where a good fraction of the hundreds of millions of dollars that go into the development of legal drugs wind up, and it is necessary because biochemistry differs very significantly across individuals.

What the makers of illegal designer drugs appear to be doing is more like a developer who says "works on my machine" and then ships. No testing, no QA, no coverage... just ship based on a single working instance in a particular environment. That's a recipe for disaster, and while the disasters are mostly recoverable, the process is fraught with risk.

This does not mean that making it illegal will change anything, because near as we can tell from the data the law barely changes human behaviour. Making abortion illegal does not change it's rate but just makes it unsafe. Making murder legal would not result in a vast increase in the rate of murders--it would result in blood-feuds and other mechanisms that the codification of law was designed to prevent. People don't refrain from murder because it's illegal (for the most part) but because they believe it's morally wrong. The law follows from that widespread moral belief, not the other way around.

So legalization and regulation may well be the best way to go, but given the ordinary standards of drug development that might create an underground grey-market where things are almost as bad, safety-wise, as they are now. A carefully targeted criminalization, that focuses solely on drug makers rather than distributors or users, might be a better solution. So long as we keep in mind that the goal is to minimize harm, including the harm done by law enforcement.

For example, plenty of people involved with developing Vioxx bought tons of it before it was removed from the market, because it was such a good nsaid. These people decided that their mode of use wasn't problematic, or that the benefits of using the drug far outweighed the possibility of adverse reaction. While the Market and the FDA decided the drug should be pulled, the people who stockpiled it are certainly more informed than most medical doctors.

If LSD were trialled for psychotherapy today, it would probably be rejected on the grounds that it could make crazy people experience severe adverse effects.

With most novel recreational drugs, there's plenty of "phase 4" anecdata which suggests safety, at least in the short term and at cautious doses. Really nasty adrs usually show up fairly quickly, albeit at the expense of a few lives. If "legal" (nonrecreational) drugs could be put directly into phase 4 testing, drug development would be so much easier-- Animal models are a really crappy substitute for humans, especially with CNS stuff.

I suppose it's a balance of Bad Big Pharma poisons us vs. Bad Big Pharma doesn't make cheap/new drugs...

I've tried on numerous occasions to debate with individuals that hold such an opinion. Once you point out the obvious error in their reasoning, they quickly move the goal post. It then becomes more about "protecting" productive society, and the slippery slope argument that everyone will devolve into "addicted, unproductive and unhealthy junkies". Making out to seem like we want society to burn and be ruined, when in actual fact we just want to allow individuals to be free to do with their bodies as they please, because there is no moral right by others to prevent them from doing so.

I've nothing against the yearning to alter one's consciousness, however temporary it might be. But alcohol might be the only way to do it without assuming either great personal risk or great moral hazard. And alcohol can be so, well, boring. One of the great sadnesses of the world we live in.

• makes people vomit • makes people fight and argue with each other • is incredibly easy to take to excess • physical addiction entirely possible • damaging to liver + kidneys

Cannabis:

• makes people lazy • makes people hungry • makes people generally friendlier • capable of curing cancer as well as many major diseases • not physically addictive

So wait, what?

False dichotomy in the modern age, unfortunately. You have no way of knowing what's in that illegal drug. It might be (and often is) exactly the same stuff.

Of course, we could eliminate this ridiculous dilemma between the risk of novel side effects with "designer drugs" and the risks of illegality with the better-known recreational drugs, simply by making those drugs legal, although that will increase usage. That also has the additional benefit that it removes much of the stigma and danger from things like hobby chemistry. So far, it seems to be working well in Colorado and the Netherlands.

That is not to say you can't draw a logical distinction between the two that supports banning or strictly regulating the production and sale of one, while leaving the other alone - in fact I would say you've got a good start on doing that already. However, the distinction is subtle, and will be totally lost on a population that has had anti-drug propaganda shoved down its throat by the state for the last four or five generations. Any nuance in your argument will be seized on by drug warriors to justify banning the sale of e.g. marijuana or peyote, etc., and bring offenders into to the ever-growing all-consuming all-powerful prison complex.

There are 66 cannabinoids and 480 known compounds in marijuana. It's hard to know exactly what is happening. I do support research for THC+CBD oil treatments to fight cancer cells. But if you are suffering through radiation or chemo, I would much rather have the full spectrum of marijuana to deal with it.

And it turns out that vaporization is not only better for cannabis but tobacco as well, hence the e-cigarette craze.

The only reason that was able to happen is because the legal and ethical restrictions were looser than they are today. In the meantime, several other such experiments have ended with the deaths of the chemists who decided to self-experiment.

I remember reading about several specific chemists. I'll try to find them. Maybe someone else can point them out while I look.

EDIT: I'm wrong.

It's interesting to realize that it did require human experimentation in order to discover, though. But maybe I'm flat out wrong about chemists dying through self-experimentation.

Regardless, I'll start re-checking my sources before saying anything.

Yeah, in hindsight it is, but if we try to remember history of pretty much every discovery — it all actually required some human experimentation. Everything starts from accidentally noticing something — something unknown and thus potentially risky. I remember how funny it sounded back then in school when somebody was telling about Volta checking if there is electricity by putting wires in his own ears. Because, — yeah, who does that! — right? But back then there was no other way to tell! (Of course voltage must have been really low, but still, I find it quite demonstrative.)

I like to think that this actually is the essence of science: doing apparently stupid things and foolishly risking even your own health because of sheer curiosity.

[1] http://en.wikipedia.org/wiki/History_of_lysergic_acid_diethy...

[2] http://insanebraintrain.blogspot.com/2011/07/massive-dosing-...

https://www.erowid.org/general/conferences/conference_mindst...

The closest I've heard of is the grad student who gave himself Parkinsons and later died while trying to make MPPP, but that was because he unknowingly messed up the synthesis and not because he was purposely experimenting with some new molecule.

1 alcohol maker can probably support 1000 drunks everyday. The maker doesn't have to drink, just taste a tiny bit for quality assurance.

In the same vein the chemists can never know about interaction effects.

It doesn't exactly count as he was experimenting on the chicken rather than himself, but it does sound as though drugs may have been involved.

He didn't just want to trip. When he took on the interest, he became a veritable encyclopedia on mushrooms, of various sorts and in general.

This was also back many years before the current "Maker" trend. I guess you could call him a prototype, or an example of a constant -- there has always been a certain number of these highly intelligent free-thinkers and builders.

I was never and am not into drugs. Getting to know him, however, did make my take a closer look at re-evaluate much of the simplistic "drugs are bad" indoctrination I'd encountered and been force fed growing up.

Just as life and current circumstances have taught me to more carefully re-evaluate other tropes such as "paying one's dues" and the "self-made man [person]".

I'm reminded of decades of research into cannabis severely stunted, so I read, by government policy and laws. "It's bad" and "because we say so" does not comport well with open and full-ranging scientific inquiry.

I just wish we could follow what Colorado has done.

This

I often get spams from these businesses selling "legal highs" or something like that.And of course you wouldnt even know what you'd be buying... they always have fancy names like "koyotte""mdmazing" or "Dragon kiss" ...

Seems like it might be the most effective idea, since, if there are legalized drugs, the majority of the drug oriented population is likely to stick to the safe, approved drugs, and, those who are inclined to push limits can easily go into research without fear of persecution.

http://publicaddress.net/hardnews/the-twilight-state-of-the-...

--edit-- I'm amazed at the quote from Caldicott at the end. WEDINOS is widely used by the NPS community to check the identity of their substances. It allows the project to map out drug emergence and for the users it provides a little safety check. For the founder to have been someone who considers drug use a disease and prohibition like an antibiotic seems to go against the open, harm-reductive effects of the service itself.

Phenmetrazine was originally banned because it was widely abused, not really because of any health reasons above and beyond the likes of dex-amphetamine, so far as I can tell, rather than anything like Fen/Phen which causes heart valve mutations.

The point being, if all substances were legalised, I think we all could easily see there being a wide range of branded drugs that might offer the same base experience with different subtleties to it. Longer and harder or short and sweet etc. You don't think so?

It's a great read. Starting out describing the evolution of drug use, and the relatively recent implementation of laws to control the substances. Progressing on to the present day, describing the point we're at now - use of TOR and dark net markets to acquire these compounds, pseudonymously, over the internet.

What's irritating is the expense of public resources bailing people out of the pursuit of the Darwin Award. Of course the same could be said for smoking, consumption driven obesity, excessive alcohol intake, etc.

The comment here regarding personal accountability sums it. I suspect if the financial disincentive is high enough on any one of these topics, people will deselect participation in said activity. Otherwise society will (or should) deselect them as beneficiaries of resources, etc..harsh, but what other practical course of action is there?

They do have unknown harm profiles, for the most part, and they may well have been designed by someone who just liked to draw in an organic molecule drawing package, but the production conditions are likely to be pretty modern.

You mean storytelling?

As for this article, the writing is OK, but I honestly wonder sometimes if these authors are being paid by the word. Take the first paragraph for instance. Replace it entirely with, "It was a dark and stormy night". Did that make the article better, worse, or no different?

Had the same information been conveyed in far fewer words, I wouldn't have had to skim over parts and would have got a lot more out of it. There's definitely a place for articles like this, but I don't think HN is that place.

I can agree though that sometimes it's hard to estimate time which you would spend on a story. I use a word-counting service (textalyser) for that, and this particular story is quite long even by longform standards: 7,800 words / 47,000 characters (with spaces).