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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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January 7, 2011

More On Homemade Street Drugs

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Posted by Derek

I wrote here about a Wall Street Journal article covering illegal street-drug labs in Europe. Well, maybe that should be not-quite-illegal, because the people involved were deliberately making compounds that the law hadn't caught up with yet.

The article mentioned David Nichols at Purdue as someone whose published work on CNS compounds had been followed/ripped off/repurposed by the street drug folks. Now Nature News has a follow-up piece by him, and he's not happy at all with the way things have been turning out:

We never test the safety of the molecules we study, because that is not a concern for us. So it really disturbs me that 'laboratory-adept European entrepreneurs' and their ilk appear to have so little regard for human safety and human life that the scant information we publish is used by them to push ahead and market a product designed for human consumption. Although the testing procedure for 'safety' that these people use apparently determines only whether the substance will immediately kill them, there are many different types of toxicity, not all of which are readily detectable. For example, what if a substance that seems innocuous is marketed and becomes wildly popular on the dance scene, but then millions of users develop an unusual type of kidney damage that proves irreversible and difficult to treat, or even life-threatening or fatal? That would be a disaster of immense proportions. This question, which was never part of my research focus, now haunts me.

Well, that's absolutely right, and it's not terribly implausible, either. The MPTP story is as good an example as you could want of what happens when you just dose whoever shows up on the street corner with that cool stuff you made in your basement lab. All we need is a side effect like that, which comes on a bit more slowly, and there you'd have it. That's one of the reasons I have such disgust for the people who are making and selling these things - they show a horrifying and stupid disregard for human life, all for the purpose of making a few bucks.

At the same time, I think that Nichols himself should try not to blame himself. His article comes across rather anguished; I have a lot of sympathy for him. But the actions of other people, especially scum, are outside of his control, and I think he's taking every reasonable precaution on his end while he does some valuable work.

Homo homini lupus: the sorts of people who see basement drugs as a fun business opportunity would likely be doing something equally stupid and destructive otherwise. Dr. Nichols, you have nothing to be ashamed of, nothing to apologize for - and, honestly, nothing to keep you up at night. You're the responsible member of the human race in this story.

Comments (40) + TrackBacks (0) | Category: The Central Nervous System | The Dark Side | Toxicology


COMMENTS

1. Henry's cat on January 7, 2011 11:39 AM writes...

I do not wish to defend the 'entrepeneurs' making and selling analogues of Nichols' compounds, but when I read your quote part of it instantly piqued me.

"For example, what if a substance that seems innocuous is marketed and becomes wildly popular on the dance scene, but then millions of users develop an unusual type of kidney damage that proves irreversible and difficult to treat, or even life-threatening or fatal?"

Remove the dance scene from this analogy and you could easily be talking about tobacco or alcohol.

You could argue that the companies peddling these tobacco and alcohol are showing a stupid disregard for human life, after all, we KNOW their products are inherently unsafe.

If people smoke full in the knowledge that they are significantly increasing their chances of dying from a number of diseases, how are they much different from purveyors of soon-to-be-illegal synthetics?

How is the 'legitimate' purveyor of deadly substances different from the back-street 'scum'? You are rolling the dice if you buy from either of them.

Tax dollars and shares in pension funds may have something to do with it...

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2. p on January 7, 2011 11:51 AM writes...

I think a little blame should be reserved for the users of the drugs as well. Buying do-it-yourself drugs from a dude at a dance club is unsafe. Those folks most assuredly have substance abuse problems, as well as many other problems, and in no way am I saying that they "deserve" such a fate. But we all do ultimately have some responsibility for what we injest/inject/inhale.

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3. Tom Davies on January 7, 2011 12:46 PM writes...

Yet another reason we should legalise drugs, making them subject to the same quality control incentives which come with any branded product.

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4. @cutlersr on January 7, 2011 12:46 PM writes...

Personally, I am not sure where I stand on "legal-high" entrepreneurs. If consumers want to make themselves guinea pigs testing not-yet-illegal molecules, that is their right. I also presume that a legitimate business would have better chemical QC than the guy with a basement lab selling on the street corner. But the business, as descried in the WSJ article, does still sounds quite shady.

I have always be fascinated by scientists like Alexander Shulgin (http://nyti.ms/MJaFR) who synthesize molecules and ingest them themselves as an exploratory / characterization process. But he wasn't pushing them for profit on the internet!

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5. Anonymous on January 7, 2011 12:49 PM writes...

I agree with #1, remove references to the "dance scene" and you could be talking about a host of modern pharma products... Fen-phen, Pemoline, Sibutramine, Thalidomide, Vioxx anyone?

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6. Joe T. on January 7, 2011 1:25 PM writes...

If people smoke full in the knowledge that they are significantly increasing their chances of dying from a number of diseases, how are they much different from purveyors of soon-to-be-illegal synthetics?

In one case, the users have at least basic knowledge of the idea that "[smoking|drinking] can kill you", typically augmented by warnings right on the packaging. I doubt the same is generally true of users of these club drugs, whose "toxicity testing" was "it didn't kill us, it must be OK" and whose packaging warning consists of "This stuff will really mess with your head, man, you gotta try it."

Which doesn't mean I have a whole lot of illusions about the ethics of tobacco and alcohol manufacturers, who as a class had to be dragged kicking and screaming to the relatively minimal measures they take now, but they're still ahead of these basement chemists.

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7. Hofmann#2 on January 7, 2011 1:46 PM writes...

I see no big problem here - caveat emptor, they are not selling it and lying by saying its something else, or trying to say its good for you, or whatever, no deceipt. As was pointed out previously, lots of bad stuff is sold and we eat it, drink it and smoke it but thats life. Some folks like to jump out of planes, some like to race cars, some like to drive motorcycles, some like to get drunk, some like to eat too much, some like to box, some like to...oh hell, you get the idea. I hate living in a Nanny state and as one of the other astute commentators here pointed out, the illegality of so many more well understood drugs is what prompted this exodus to untried substances in the first place. I never quite understand why the hell somebody cares what somebody else does to themself?

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8. Derek Lowe on January 7, 2011 3:28 PM writes...

Hofmann#2 (and the others making similar arguments): I think my problems with caring what other people do to themselves are two-fold.

On the idealistic side, I think that many of the people who take these things are not exactly informed customers. They think that they're taking something for a fun night, when they might be getting some damage that'll be with them for life. I admit, though, that club kids are not known for their skills at risk/benefit analysis.

And on the hard-headed pragmatic side, I object to having to help pay their medical bills, through my higher premiums and my taxes. (And yeah, I'm not thrilled with the bill for either alcohol and tobacco, either).

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9. Ken Bob on January 7, 2011 3:49 PM writes...

To echo Derek,

I don't like the idea of someone being high/hallucinating while behind the wheel of an automobile, tractor trailer, etc. It's bad enough with the drunks we have on the road. I've never heard any legalization proponents address that.

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10. Hofman#2 on January 7, 2011 3:52 PM writes...

Thanks for your thoughts Derek, one last refrain then I'm done (I've got a reaction to work up and its Friday!)

First, I have a hard time believing the folks who buy illicit drugs do not know that the drugs are dangerous and even more importantly, even if they did I reckon they just don't care. How many people decided not to smoke or drink because the warning on the bottle or pack or whatever. Some people have a strong desire to alter their conscious state. That is hard for folks who don't have that desire to understand but it simply is a fact. Some folks who avoid drugs get their stimulation by rock climbing, becoming president, chasing sex, watching scary movies or whatever but others prefer pursuing a more direct route. Is it safer of more dangerous one way or the other...who knows? With regard to your pragmatic argument, I have heard that before and first, I am not sure it really makes much sense because those unfortunate ones who OD and die young cost much less than if that same individual goes on, has kids who we have to pay to public educate, lives until he's 90 (think of the health care bills then!), etc. Besides, the cost argument would be an argument to outlaw alcohol, cigarettes, McDonald's and anything else that affects somebodies lifespan - freedom is too precious Derek, people can and must make their own choices.

Despite all the hype and drug war rhetoric, drugs are not as dangerous as they are made out to be. I've looked on the top 10 causes of death and don't see drug OD's listed there. The fact that some guy prefers to get his thrills in a different manner than you or I is no reason to throw such folks in jail - the drug war policy is assanine just like prohibition was and it's just as effective. Most illegal drugs are far less dangerous than alcohol. By making safer drugs illegal, we force people to imbibe one of the crappiest an most unhealthy drugs of all (drinking alcohol is one grade above sniffing toluene). I've thought much about this topic and drug legalization is the best way to go. I believe that 100 years from now people will look back at the time we are in and shake their heads, amazed that we dared to imprison folks for wishing to adjust or explore their own conscious states. I'm no liberal, just a libertarian and have faith that Man's ultimate trajectory is ultimate freedom.


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11. bill on January 7, 2011 4:17 PM writes...

Honestly, I would prefer these "research chemical" vendors to be a little more cautious with the welfare of their customers. Obviously there is a huge market for legal chemicals that mimic the effects of illegal ones, and the consumers really don't care what they could be doing to their body. But would it kill the vendor to perhaps include a page of warnings and dosage instructions? (Something thinly veiled like, 'only feed your plant 100 mg a day').

I created the wikipedia page for tert-amyl-alcohol a few years back after I discovered that it had some interesting medicinal properties (was used as a sedative back in the early 1900s). Within the last 6 months, RC vendors have been selling it online for human consumption and numerous "experience reports" have also appeared. All this activity was basically spurred by my carefully researched and cited writeup on its pharmacology on Wikipedia. RC vendors literally dissect Wikipedia pharmacology articles to find new leads.

In response to this, I double and triple-checked the dosage, duration, & tox information I had researched to make sure people weren't going to kill themselves. Lo and behold, the exact words I wrote on wikipedia are being copied and pasted to vendor webpages.

It's a crazy world out there.

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12. Hofman#2 on January 7, 2011 4:32 PM writes...

Ken Bob, real quick - lots of people get in accidents while talking on the phone, texting, etc - should we outlaw cellphones and throw their users in prison even when they aren't driving? No, we ask or require that they don't do it while driving! Further, - codeine, oxycodone, xanax, valium, etc are all legally prescribed - some folks drive while on them. Do you propose to outlaw the use of these for all purposes as well? No, you outlaw their use while driving! Legal drugs can be tested for more easily then illegal ones. By making many drugs illegal for recreational use, underground chemists come up with analogues that can't be tested for. You've just made a problem into a worse problem.

Outlawing drugs has done nothing to curb their use but it has filled up our jails and prisons and wasted billions of dollars of our tax dollars pursuing the prohibition of what is a basic aspect of human nature (the desire to alter one's conscious states). You see, there are many things that other people do that I don't agree with. For example, why should we have cars that are capable of going over 100 miles an hour when the speed limit in every state is much lower - people that speed put all of us at risk and there is a solution, right? Why do we allow people to have sex outside of marriage- AIDS and other venereal diseases are transmitted that way and we have to pay for that behavior. Why are knives legal and especially guns? Even though they have legitimate uses, thousands of innocent people are killed every year. But you see, even if I don't believe or use one or all of these things, you might.

I've heard people at parties, half in the bag from alcohol complaining about those weird and crazy drug addicts! Alcohol is way more antisocial, way more debilitating than most of the illegal drugs but we tolerate it because the majority are familiar with it. I guess if you take your drink from a glass your fine but if you take your drink from a pill or puff you should go directly to jail (where you really do become my problem). I'm out of here for real this time - gotta go pick up some beer, its Friday!

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13. Ken Bob on January 7, 2011 4:47 PM writes...

Hofman#2, We're going to have to agree to disagree. I understand your arguments, but I don't think that legalization is the solution. Making mind altering drugs illegal is the lesser of two evils when the alternative is legalization. Even though I'd like it to be my right to be completely libertarian (which for many sometimes slides to being completely libertine), I recognize that some things I can do to myself can injure others, physically, economically, emotionally, etc. Rights come with responsibilities, which is so often forgotten. If they were responsible individuals to start with, they wouldn't be exercising the right to use.

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14. NWO on January 7, 2011 4:47 PM writes...

The Corporatocracy controlled by the oligarchs sure hates competition, huh Derek?

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15. Nile on January 7, 2011 6:54 PM writes...

I'm going to make a lengthy point about education and chemistry, so if you don't like that kind if thing, skip to the next comment now...

I followed the link on MPTP because it kind of 'rang an alarm bell' and I ended up reading one of the scariest things I've ever seen on the World Wide Web:

" we had one ambitious boss and at the meeting she proudly presented series of MPTP analogs with substituted indole in place of phenyl in MPTP . She looked at me as if I was making stuff up when I mentioned it ."

I've had bosses like that: they're the boss, they're right and you're wrong and that's the end of the discussion. Want to be sidelined and marked on your review? Carry on disagreeing. Imagine being female and having an influential MALE colleague patronise you when you raise that kind of concern...

Now look a bit deeper. Me, I have some lab training related to public health work and part of a medical degree, but the reason I've heard of MPTP is that I was a curious teenager, engaged in science, who saw the BBC Horizon / PBS joint-production documentary on 'The Frozen Addicts'.

The majority of doctors I know - my former fellow-students - do not know about it: they lack intellectual curiosity and can be considered 'trained, but not educated'.

Shocking, isn't it... But it's terrifying that a graduate chemist wouldn't know. The big deal about a chemistry degree is BREADTH - not just reciting a few (or many, many!) synthesis paths, but a deep knowledge of the underlying principles and a wide knowledge of the folklore and the anecdotes in the 'background reading' that makes chemistry as much a craft and a community as the 'Art or Science' of Medicine.

The chemist in that anecdote probably had a pretty good degree and a DPhil... Based on an intensive education, good retention, and a total lack of the intellectual curiosity and interest that drives effective 'background reading' and a grasp of the subject in its breadth.

I see a lot of these golden children in the consultants' teaching round on the wards, emerging from the hothouse of the preclinical degree with every accolade, and worse than useless when presented with a case requiring insight and a little bit of lateral thinking...

Do you, as chemists, recognise that picture in the graduates and postdocs turning up for work and doing brilliantly in their 'management potential' work appraisal?

Chemistry has many, many MPTP incidents awaiting your discovery: I hope that you survive the experience. My advice is that you take the 'Pink Slip' or the P45 and look for work elsewhere if you have to call out a colleague (or a manager) who risks their life and yours through arrogance and ignorance.

Meanwhile, I could synthesise most and maybe all the things that you do... With careful notes and some guidance for the first few runs. Yes, my lab technique really is that good - you could say that it runs in the family. But I'm not a chemist and thank God I've got the wisdom not to try! Being able to do things isn't the same as knowing what you're doing, let alone knowing what you might be doing. That's the difference between education and training, if I need to spell it out.

What the hell are all these follow-the-recipe lab technicians actually *doing* in their bootleg laboratories? Most of them have no idea of the risks they're actually taking and I am astonished that fatalities are, fortunately, very rare.

Would anybody from the organophosphate field care to make an estimate of the likely prevalence of long-term health effects, based on a crude extrapolation of the (known, I hope) ratio of immediate Vs delayed toxicity effects in better-studied compounds and the known (but probably under-reported and incomplete) statistics on prompt mortality from 'designer drugs'?

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16. anon on January 7, 2011 7:23 PM writes...

@Ken Bob. Smoking dope is well proven to lead to less accidents (slower reaction times, but less aggressive driving). If you knew that would you change your opinion? Is your opinion based actually on the idea of safety or distaste at the idea of illegal drugs?


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17. Got_QSAR? on January 7, 2011 7:27 PM writes...

Another serious problem associated with 'designer drugs', especially the hallucinogenic variety, is their propensity to hit 5-HT2B (as agonists). Chronic 5-HT2B activation can lead to valvular heart disease (think fenfluramine).

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18. anon2 on January 7, 2011 8:52 PM writes...

@anon #16

Smoking dope is one thing, but when one mixes it with alcohol, the compensation mechanisms that one might use with THC alone are no longer used. In any case, if one has only been smoking dope, I'm not really sure I would want you on the road, regardless. It isn't like driving slower than the rest of traffic is somehow "safe".

Also, speaking for myself, I am unaware of any right to mind altering drugs taken recreationally explicitly or implicitly. There is no right for a private citizens to manufacture or own something dangerous like chlorine trifluoride. Sure, some people could handle it properly if they owned the proper equipment and knew what they were doing, but the 25% of the population with no clue as what they would be doing with the stuff or how to use the stuff have no business near it. Besides how often would anyone want to be doing the equivalent of leaving their neighborhood weekly once or twice a year because an idiot got in over their head? Same deal with people driving impaired. Most people are not idiots, but when it comes to legalization of drugs, there are enough stupid people who would misuse a product to make legalizing drugs just not worth the risk to others.

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19. Ken Bob on January 7, 2011 9:17 PM writes...

Maybe pot does have reduced accident rate, but again, I'd not want to be on the road with someone who smoked it as they are taking their lives and the lives of others in their own hands with an altered mental state. What about the signs I see all over: "Kids Dart" - yeah I think a reduced reaction time is good (that's sarcsm) for that kid chasing the ball into the street. Many wanting to legalize drugs aren't stopping their arguement at pot. Cocaine is just as big a trafficking/crime problem. So, want somebody on the road doing an acid trip? High on crack? Instead of stopping at the bar on the way home, lets just snort a line at the office or drop a 'lude before we rev up the engine. Legalization would indicate to many that the government now thinks its safe, or else it wouldn't be legal (look at what the FDA makes us go through to put a drug on the market!). The thought of all that scares the bejesus out of me. We've got too many idiots out there on the road already. No point in adding to the number. I think drinking and driving penalties aren't tough enough, so you can't say that its not any worse than where we are. We can improve that too.

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20. Sad Chemist on January 7, 2011 10:41 PM writes...

I work for a contract outfit in the Midwest. We made alot of money these past two years off "legal high drugs".

When the projects started coming in a couple of years ago we were told by management it was shipped to Europe for making incense. Of course, something didn't quite ring true so we got online and discovered the true end use of what we were making.

Our boss, a complete jerk, believes he has no liability because he thinks he can hide behind one sentence on the label of these bottles: "not for human use".

I have to say that when I was growing up and studying to be a chemist I always thought I would use my synthetic knowledge for good. Cure cancer or something. Never in a million years did I think I would essentially become a drug dealer and worse, make a living off something that could kill people. The sad fact is these compounds have been the only thing standing between me (and my colleagues) and the unemployment line.

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21. Spiny Norman on January 7, 2011 11:30 PM writes...

That's a totally uncalled-for insult to wolves, Derek.

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22. gippgig on January 8, 2011 1:03 AM writes...

"They think that they're taking something for a fun night, when they might be getting some damage that'll be with them for life." (#8) - the same comment can be made about participating in sports (admittedly the hazards of sports are known unlike untested designer drugs).

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23. stickfigure on January 8, 2011 8:19 AM writes...

"Maybe pot does have reduced accident rate, but again, I'd not want to be on the road with someone who smoked it"

Oh come on, you're a scientist. You can argue with the matters of fact (do pot smokers/cellphone talkers/makeup appliers/etc have a reduced accident rate?) but once the statistics line up, you can't just throw out the inescapable logical conclusion just because you have an emotional bias against it.

If it turns out that thc-intoxicated people do not have a higher risk of causing accidents (something that would need to be verified), there's no rational basis to prevent such folks from driving.

At any rate, this DWI argument is a red herring. Legalizing drugs does not equate to legalizing driving while intoxicated. Just as abstinence-only education fails to prevent std transmission and pregnancy, it shouldn't surprise anyone that abstinence-only drug policy fails to prevent improper use. Like it or not, human beings have sought to alter their mental states for thousands of years, so we should be equipping folks with the knowledge and attitudes that minimize harm. Equipping kids with ignorance helps no one.

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24. Ken Bob on January 8, 2011 11:36 AM writes...

One last comment and I'm done. Rhetorical question: As many of us are working hard in the pharmaceutical industry trying to get drugs on the market that might actually help people, why are so many on this blog advocating the legalization of neurotoxic substances whose toxicities would not pass FDA scrutiny if contained in an NDA submission for a prescription medication?

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25. aairfccha on January 8, 2011 12:47 PM writes...

This is what happens when the known, (relatively) safe drugs are illegal. People WILL ALWAYS try to get high, using what's available.

Legalize, regulate, educate.
Prohibition still doesn't work and never will (unless a good substitute is available, then it might be possible to push the users towards that).
The War on drugs is failing for 40 years now. What is needed to end it?

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26. Curious Wavefunction on January 8, 2011 5:11 PM writes...

Whether is a product is successfully banned is a simple matter of economics, of whether the cost/benefit ratio is high enough for people to not care too much about it. Try banning cars which kills tens of thousands every year, or try banning kitchen knives. The only reason these products can't be banned is because the benefit is too high relative to the costs. The same goes for alcohol, and it's going to always be the same case with pot and some other drugs. The benefits are just too lucrative compared to the costs for most people. That being said, I agree that it's stupid and dangerous for producers and consumers to put untested products out on the market.

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27. Curious Wavefunction on January 8, 2011 5:11 PM writes...

Whether a product is successfully banned is a simple matter of economics, of whether the cost/benefit ratio is high enough for people to not care too much about it. Try banning cars which kill tens of thousands every year, or try banning kitchen knives. People will laugh at you. The only reason these products can't be banned is because the benefit is too high relative to the costs. The same goes for alcohol, and it's going to always be the same case with pot and some other drugs. The benefits are just too lucrative compared to the costs for most people. That being said, I agree that it's stupid and dangerous for producers and consumers to put untested products of uncertain purity out on the market.

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28. HK on January 8, 2011 6:36 PM writes...

KenBob - it's not about legalizing as it is about decriminalizing. There are a lot of things that aren't criminal - eating a battery, sticking fingers into electrical sockets - that we are educated about early on and strongly encouraged to avoid. The same could be done with street drugs.

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29. Jose on January 8, 2011 9:26 PM writes...

"Chemistry has many, many MPTP incidents awaiting your discovery: I hope that you survive the experience."

So true. Combi chem gave many opportunities for this to happen, only a few were reported, many more were under the radar.... we found out the hard way that small fused indole libraries are not be toyed with.

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30. Jack Bauer on January 9, 2011 1:45 AM writes...

Call me a monster, but I have zero sympathy for people who smoke or inject white powders.

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31. Dan on January 9, 2011 2:27 AM writes...

Ken Bob: Making stupidity illegal won't cause everyone to become smart. Prohibition of alcohol failed because people wanted to drink alcohol; if the legal, presumably uncontaminated stuff isn't available, they'll take their chances with the bathtub moonshine. This is no different; all the War on Drugs has achieved is to make sure drug dealers get better pay because they don't get competition from non-shady sources and since they can't exactly submit samples to any respectable lab for testing (and probably wouldn't care to even if the price wasn't a one-way ticket to the slammer), nobody has any idea whether there are impurities or what the long-term effects of any of them is.

Legalize it, regulate it (no sales to minors, rigorous testing to avoid contamination, short- and long-term risks documented on the package), and you take the market away from the basement labs because you can get stuff that's (relatively) safe from reputable sources instead. If they're going to get high anyway, you might as well make it as safe as possible for them to do so.

I wouldn't touch the serious mind-altering stuff myself even if it was legal, but assuming they're not operating heavy machinery on public land or roads, what others put in their bodies is not my business. As long as people know the risks, it's their decision whether they think the benefits outweigh he risks.

(BTW, not a chemist, but a relatively long-time reader drawn in by a link to the famous ClF3 post.)

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32. Zigzag on January 9, 2011 2:08 PM writes...

Instead of worrying about prevention of use and making the act of use illegal in itself, it is much more straightforward to adopt a swift, direct & stern penalty system for causing accidents etc. while intoxicated (with whatever it may be, cocaine or alcohol or the newest CNS stimulant). No excuses, no three-strike rules, none of the 'i blame the society for not educating me properly to avoid drinking and driving' business.

It should be perfectly fine for people to smoke dope and *walk* (or take a bus, train, etc.). It is also fine if they choose to drive, as long as they do not cause accidents. If they do, however - they should be punished severely, including the prompt death penalty (without the 10-year wait in jail and endless appeals) in cases where their unsafe behavior caused death or severe injury to others. I am willing to bet that it won't take very long to balance things out and for the less intelligent drug abusers to be taken out of the equation - and I am also willing to bet that the level of harm to innocents during the re-equilibration period will be less on average than what's going on now, with all the rules and laws prohibiting the use, rather than punishing the consequences (it's enough to remove the collateral damage to innocents caused by violent disputes between illegal drug peddlers to even out the score).

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33. GreedyCynicalSelfInterested on January 9, 2011 6:52 PM writes...

Why don't these people just start the next "Airb@rne, Inc."? You do a lot of marketing, make vague but true claims and watch the money roll into the bank!

It's sleazy, but no one dies from it.

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34. AJL on January 9, 2011 7:34 PM writes...

Dan is right on the money where he says:

Prohibition of alcohol failed because people wanted to drink alcohol; if the legal, presumably uncontaminated stuff isn't available, they'll take their chances with the bathtub moonshine. This is no different; all the War on Drugs has achieved is to make sure drug dealers get better pay because they don't get competition from non-shady sources(...)

The behavior of taking intoxicants has been a universal in human history. Whether or not we believe that's fortunate, it's foolhardy to think we can make it go away instantaneously with the passage of laws - any more than I could outlaw the cognitive biases that likely lead to this belief. It's a thing human beings often do. Not all cultures, but many, have successfully had controlled access traditions for mind-altering drugs - whether that's an adulthood rite of passage, or exposing children to small amounts, or a class of individuals trained to deal with them.

The real shame is that, while we haven't successfully stopped people from using mind-altering drugs, we've successfully stopped people from using them in ways that engender minimal risk.

It's very much like the school of thought that prevailed in relation to AIDS for many years: if social mores don't approve of what people are doing, the people doing it must deserve illness and death -- even when this could be prevented by condoms and education. An abhorrent way of thinking that leads to abhorrent results.

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35. john on January 10, 2011 12:09 PM writes...

I'm a power lifter and a chemist. When I was in grad school I was approached 5 times at by different people looking for "the good Sh*t" steroids. One was an NCAA athlete. I turned them all down but I tell you the money offered was impressive, it would have supplemented my stipend really well. Given the level of supervision I know I could have gotten it done fairly easily. One of the people told me that he had previously purchased from another grad student but that student had graduated.
Of course I also know chemists who were buying ritalin from the many dealers you can find around campus to get through their prelims and quals let alone get the grades to get into grad schools. Thats ok though because the abuse of these kinds of drugs is usually by rich kids who are trying to get an edge.

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36. AK07 on January 11, 2011 8:28 AM writes...

Derek: "And on the hard-headed pragmatic side, I object to having to help pay their medical bills, through my higher premiums and my taxes. (And yeah, I'm not thrilled with the bill for either alcohol and tobacco, either)."

If that were true the right solution would be not forcing you to pay for their medical bills not outlawing the drugs. But it's not, at least not in the case of tobacco, it has been showed that its smokers who pay for everyone else, since the fact they die early more then makes up for their medical bills. The same could hold in other cases.

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37. Trottelreiner on January 11, 2011 7:11 PM writes...

Well, with the driving under influence story, that may need some further discussion; concerning cocaine, dopamine reuptake inhibition is also the mode of action of methylphenidate, and even though the 'manual' in the package advises you not to handle any machinary while using it, it's quick to add that in ADD people it might improve driving skills; having limited experience with cars lately (nobody wants to lend theirs to me *g*), I'm in a limited position to answer that, but thinking stop-and-go traffic to be a nice analogy for a TOVA test and having done my fair share of scratching the metal, there may be something to it. And then, since concentration problems are likely to be not a clear-cut issue, but a continuum, it may lead to better driving in many, though it'd impair others without them noticing it thanks to euphoria. Also note there may be problems in tired people and like, but then, there is caffeine, too.

For those objecting, the US Air Force says it uses amphetamine, a compound with similar, though not identical action without major problems, so well, either the Air Force is a bunch of liberal lefty pussies, or we need to re-evaluate some of this 'War on certain drugs' rhetoric. Personally, I wouldn't use amphetamine, but that's another story.

Concerning the original article by Nichols and the problems his little children , the problem with the RC market are not so much that most 5-HT2a agonists are often 5-HT2b agonists too, because by the point the 5-HT2b agonism becomes a problem, the tolerance to the psychedelic effects has already kicked in, like after about a week of continuous use. With the compounds created by Nichols, like 2C-B-DFly and like, is that they are potent full agonists, while LSD and psilocin were partial agonists and/or not so potent. Which leads to nice effects in overdose, like vasoconstriction and hyperthermia you don't see that much with LSD and psilocin.

Another example might be his research into serotonin releasers, like MTA or the aminoindanes; most of this research was to get 'non-neurotoxic' MDMA substitutes, where 'non-neurotoxic' might mean 'not so neurotoxic', which is one of the problems; the second is that the SAR for the various membrance transporters like SERT and VMAT overlaps with the one for MAO A and like, which was a problem in MTA, see serotonin syndrome.

The main problems seem to have been with the cathinones and some synthetic CB1 agonists, where with the CB1 agonists like in 'Spice' and like, the problem was similar as in psychedelics; THC is a partial agonist, and it's active metabolites linger around for some time, so you have a ceiling effect for the dosage, and withdrawl sysmptoms are likely mild, if you're not using a CB1 antagonists (AFAIK there was some research with rimonabant about this, the results were...nor pretty). With spice and like, that's not necessarily the case, first of, some people have raised the possibility of an enhanced frequency of panic attacks and like, reflecting their full agonism, and second of, if someone smocked through a weekend and stops using it, they might experience withdrawl, while with THC he'd have some resiual effects by metabolites, not nice when using machinary, but well, maybe better then depression.

With the cathinones like mephedrone and like, IMHO there is a possibility of neurotoxicity with all monoamine releasers, though the degree varies somewhat, see plain amphetamine, methamphetamine and MDMA. And then, a related chemical, bupropion, is used as an antidepressant and might be neuroprotectant, so, well, choose your liking. Also note there is again the relation to other monoaminergic systems, given the slower build-up of tolerance and the usage patterns seen, agonism at 5-HT2b would really be a concern here, but then, we don't know anything about this stuff.

That's not to say the old street drugs are more benign than the new synthetic entities; e.g. in cocaine, one of the culprits is the interaction with ion channels in the heart, an interaction not shared by some new tropanes. With opioids, buprenorphine is a partial agonist, while morphine and its notorious diacetyl ester are full agonists, I don't know how this translates to safety. but in the case of the CB1 agonists, extrapolating from THC to the AAIs might be foolish, there is AFAIK no known instance of a lethal acute THC overdose, but full CB1 agonists like HU-210 can be lethal.

What it all boils down to is that the current RC market is regulated by three requirements, a)it's effective, b) it's legal and c) it's in the cognitive, synthetic and economic reach of the manufacturer. Where ideally, there'd by something like a risk assesment in this equation, but well, not so. Personally, I think legalisation'd be the best option, since outlawing any mindaltering substance would be have strange results, OK, changing Bonhoeffer's famous quote to "...and when they came for my cup of Dajeeling Tea, there was no one left to speak out for me" would be bad taste, but well, so what.

Oh, and about the indolic MPTP analogue, even if it's a MAO substrate, it might still be relatively benign; AFAIK MPP+ has to interact with some mitochondrial proteins of the breathing cascade, so if this stuff doesnt, who knows. Though I definitely would bet my substancia nigra on it.

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38. Trottelreiner on January 11, 2011 7:17 PM writes...

Err, sorry for the grammatical errors and like, I'm in shutdown mode, if you excuse me...

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39. Dale DeWitt on January 13, 2011 4:48 PM writes...

It's good that chemists are looking at this issue of effective legislation. Most have their tails between their legs for sundry reasons to behold. Chemists must be honest in all walks of life. This finding is no exception

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40. Clemmie Affelt on June 21, 2013 9:12 AM writes...

Congrats Chelsea. I used to be so hoping we were likely to pull it off, but unfortunately it wasn't to be.

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