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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: Twitter: Dereklowe

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November 1, 2010

Drugs At Home

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Posted by Derek

This article reminds me of the "designer drug" era in the 1980s. The Wall Street Journal profiles one of the many European chemical entrepreneurs making a fortune by synthesizing and selling new psychoactive drugs. And they're all labeled "Not For Human Consumption", so hey, everything's perfectly legal. Until the authorities ban the specific substance, naturally, and then he moves on to another one down the list.

As someone who doesn't see a new chemical structure go into humans until years of testing have been done, you can imagine what I think of this. The small amount of amazement I feel is completely overwhelmed by contempt for anyone who would dose people with an untried CNS drug. Oh, but he's not dosing anyone, is he? All he's doing is selling them little vials of white powdery stuff for $30/gram, and it says right on the label that they're not supposed to take it. Right? How people like this sleep at night is a continuing mystery to me.

Making new psychoactive drugs is not that hard. There are plenty of chemotypes out there that will drop you right into the CNS receptors. In many cases, it looks like this guy and his ilk are hanging single-atom changes off of existing drugs. They also monitor the chemical literature, specifically mentioning papers by David Nichols of Purdue, who's well aware of what's going on (and has the same reaction I do). No, there are plenty of small changes to ring on known scaffolds; it's not like anyone's having to invent any new chemical classes here.

So, how do they make these things in quantity? The article treats a rota-vap as an exotic piece of equipment, so we're not going to learn too much from it. But I imagine that there's a lot of used lab equipment floating around, which must help. But the article also mentions that this particular business has labs in the Netherlands and Scotland, outfitted with custom stainless-steel gear made by a welder, so as to not draw attention by buying standard chemistry apparatus. (This is as good a time as any to mention that one of the things that irritates me about these people is the way they make owning any kind of chemistry equipment at home instantly suspicious in the eyes of the law).

That takes a back seat, though, to my feelings about the other aspects of this business. I'm not, admittedly, a good person to ask about recreational drug use, because I don't use any. I have what I think are well-justified reasons for avoiding the whole spectrum, from alcohol on up. The more I've learned about brain chemistry, the less inclined I am to mess around with it.

But even if you take a more lenient attitude, I don't see how the sort of business that this article details can be excused. Advocates for decriminalized various drugs often make the point that we know what their effects are, and that society would be better off dealing with them than dealing with the effects of trying to suppress the drugs themselves. They may be right, actually - I haven't made up my mind about that one yet - but this line of thought can't extend to the new-drug-of-the-month-club. We don't know what the effects of these substances are, what neurological damage they might do, and what other side effects they might have. That's for the customers to find out! Here's the safety testing method this moron uses:

Mr. Llewellyn, meanwhile, is unfazed. He boasts that his safety testing method is foolproof: He and several colleagues sit in a room and take a new product "almost to overdose levels" to see what happens. "We'll all sit with a pen and a pad, some good music on, and one person who's straight who's watching everything," he says.

Well, fine, then. Foolproof! This sort of thing shows that nothing is foolproof, because fools are just too ingenious. I'm ashamed to share a phylum with these people, much less a scientific discipline.

Comments (53) + TrackBacks (0) | Category: The Central Nervous System | The Dark Side


1. Will on November 1, 2010 7:59 AM writes...

Kind of reminds of the stories from the prohibition-era US - people were so desperate for alcohol (the ethyl variety) they tried all sorts of home brewing/buying from nefarious characters - a bunch of people ended up going blind or worse from all the crap they ended up taking [1]

Derek, I think your paragraph about decriminalization misses the point a little bit, with legalization the market for the molecule of the month would get much smaller. the vast majority of drug users would be content using the substances for which a safety profile has already been established

[1] - a recent book entitled "the poisoner's handbook" by deborah blom gives a decent account of all the junk people were drinking during prohibition. the book itself is more of a history of the development of forensic medicine/chemistry in NY. it's an okay read, but some of the chemical errors within are cringeworthy

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2. SP on November 1, 2010 8:27 AM writes...

Well, isn't the point of decriminalization that you don't need "new-drug-of-the-month-clubs" to skirt the laws, you can just use the existing well-known and less potentially dangerous stuff without fear of arrest? I didn't take you for a pro-legalization guy, Derek, but that's the argument you've made.

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3. rcyran on November 1, 2010 8:33 AM writes...

Well, there is at least one (unfortunate) bright side to this idiocy. History suggests we might learn a bit more about the brain if these chemicals damage specific parts of it.

I seem to remember you posted something on MPTP before, Derek. For those that have forgotten.

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4. Wavefunction on November 1, 2010 8:50 AM writes...

He and several colleagues sit in a room and take a new product "almost to overdose levels" to see what happens

And speaking of Darwin Awards, did you know that this year they handed multiple awards out?...

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5. Ex - GSK on November 1, 2010 9:43 AM writes...

This seems as good as any other method to trim the human herd a little.
If you are stupid enough to take something made in a garage somewhere in the world, you get what you deserve.
With there kind of manufacture and testing regulation, surely they are working for GSK, or will be very shortly

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6. Karen on November 1, 2010 9:58 AM writes...

When I was in grad school, I worked on a project involving deprotecting methyl ethers. A few years later, I did a web search for my name and I ran across a web site that described ways to synthesize designer drugs. To my surprise, they cited my paper! Evidently it was a great method for deprotecting morphine. I wasn't sure whether to be pleased that someone read my paper or appalled at how it was being used.

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7. chucky on November 1, 2010 10:04 AM writes...

With all the recently unemployed medicinal chemists I am guessing this is only the beginning. Before we make too much fun of this fellow's testing methods, let's recall the way Albert Hoffman discovered LSD. While Albert's first experiment may have been accidental, his subsequent exposures were not.

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8. milkshake on November 1, 2010 10:07 AM writes...

more than the addiction, I would fear acute toxicity. The fact that a substance does not kill people sitting around in a dimmed room and taking notes does not mean it won't drop someone with congenital heart condition or someone who had few drinks and got dehydrated from dancing in a club, or is just predisposed to malignant hyperthermia.

I guess these dudes just want to create new street drugs, earn the bragging rights and make living from it. Sooner or later some moron will whip up a batch of 3-methylfentanyl for profit and kill lots of people with it.

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9. retread on November 1, 2010 10:14 AM writes...

Bravo Rcyran: MPTP taught us a ton about Parkinsonism and about mitochondria to boot. People went from normal to having to be fed by someone else (because of their severe Parkinsonism. They were not comatose) after one (or a few) doses of the stuff. MPTP also showed that a lot of the long term side effects of L-DOPA (on off effect, dyskinesia) were not side effects in the usual sense, but were really due to loss of the dopamine neurons (which we presently have no way to stop). The unfortunates taking MPTP developed dyskinesias etc. right away.

Somewhat along these lines, the cannabinols give me the creeps. They are so lipid soluble (which means that they will persist in brain) that it was exceedingly hard to find the receptor(s) for them (CB1, CB2, . . ) because they bound to membranes so avidly.

It usually takes people a long time (weeks) to feel completely normal after general anesthesia in my experience. While it may in part be due to surgery, the lipid solubility of all general anesthetics probably has something to do with it.

This is something to keep in mind when listening to the medical marihuana debates.

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10. Anonymous on November 1, 2010 10:22 AM writes...

" this line of thought can't extend to the new-drug-of-the-month-club"

Isn't that kind of the argument? Kids are going to take stuff anyway, so let them take stuff that has been studies, that is produced in clean environments, so you don't get the drug club of the month stuff? A viewpoint that is abhorent in the US, which can't even stomach giving clean needles, but those ultra liberal Swiss do pretty much that with giving out clean heroin to addicts.

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11. Meh on November 1, 2010 10:30 AM writes...

If you want to make new novel psychoactives and test them on yourselves, go for it,to each his own, live the shulgin lifestyle, worked out great for sasha. However, everyone and their dog knows these designer drugs are targeted towards teenagers.

So... Make them all legal, with ID for 21 and have heavy fines for supplying minors.

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12. You're Pfizered on November 1, 2010 10:34 AM writes...


I understand completely.

I put together a paper a decade or so back that unintentionally (and unknowingly) included the synthesis of cathinone from that article. Didn't realize it until our chemical repository folks called me and asked me why I made it and if I had any more material laying around!

Sad thing is, it was the most concise chiral synthesis of that molecule that I was able to find. I should have published it in a better journal!

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13. darwin on November 1, 2010 10:36 AM writes...

natural selection at its finest

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14. RM on November 1, 2010 10:52 AM writes...

Derek, you aren't in the same scientific discipline as they are any more than Sean Connery, Marlon Brando and Katherine Hepburn are in the same profession as Ron Jeremy and Jenna Jameson.

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15. Nick K on November 1, 2010 11:20 AM writes...

The "father" of all these phenethylamine-based psychoactives, Dr Alexander Shulgin, is still around and in good health at 80 plus. He ingested every one of the dozens of compounds he made to report the effects. You can read about his self-experimentation in his book "Phenethylamines I have known and loved".

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16. Anonymous on November 1, 2010 11:31 AM writes...

As skeezy as it is, this guy's still safely in the bounds of the categorical imperative. He very clearly uses and enjoys using drugs, regardless of what their safety might be. If he wasn't running the business, he's the type of person that would likely be a customer. If people who use unsafe drugs want to make and sell unsafe drugs to each other, I don't have much of a problem with it, provided everyone knows the risks they're taking. And if that awareness is lacking here, it's a question of education, not ethics.

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17. NJBiologist on November 1, 2010 11:43 AM writes...

@3: Absolutely. Kind of makes you wish the reporter had heard that story.

For anyone with some understanding of controlled substance law: how on earth is this NOT covered under the "Treatment of controlled substance analogues" provision and therefore included under Schedule I?

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18. startup on November 1, 2010 11:51 AM writes...

"We don't know what the effects of these substances are, what neurological damage they might do, and what other side effects they might have. That's for the customers to find out!"

Isn't how on regular basis it works out with big pharma offerings as well?

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19. Frank Adrian on November 1, 2010 11:52 AM writes...

I view this as another unintended consequence of the worldwide "War" on drugs. The bottom line is that people want to occasionally and temporarily modify their consciousness for recreational purposes. It would be better if this were done with tested and legal substances having fewer side effects. However, licit research on this front that might lead to better substances than currently legal drugs is so constrained and stigmatized that any research (as well as commerce) in this area is pushed underground. Allow legitimate pharmaceutical houses to actually search for better, safer recreational alternatives and you won't have this happening. Besides, the line between drug companies altering neurochemistry for cure/maintenance of disease and lifestyle issues became awfully obscured with the coming of SSRI treatments for just about every anomie of modern life - crossing the line to recreational sales wouldn't be much different; the point is to allow the consumer of the drug to have a better time with their life. Of course, that would also require that the society grow up and start accepting that sometimes people want to alter their consciousness and that it is OK to do so. So of course, this won't happen.

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20. TFox on November 1, 2010 11:58 AM writes...

I liked the plot of the research productivity of this industry -- getting 20 NCE's onto market per year, based on a very low investment, as compared to what, about 40 or so for all of traditional pharma? Shows what an impact regulation has.

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21. CR on November 1, 2010 12:02 PM writes...

"He boasts that his safety testing method is foolproof: He and several colleagues sit in a room and take a new product "almost to overdose levels" to see what happens."

Question: How did they determine the "overdose level" since they state they take to "almost overdose levels"? Has one of them calculated the overdose level - and by "calculate" I mean actually overdosed since that would be their version of determining the level.

On a side note: I used to work for a large pharma company and was looking back through the microfilmed lab notebooks for a procedure and came across some old analytical reports and one of the boxes was "taste" - and most of the compounds had this filled out...

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22. Vader on November 1, 2010 12:09 PM writes...

You ask how these people can sleep at night.

Then you describe their testing methods.

The real question is how they can be sure they'll wake up in the morning.

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23. Anonymous on November 1, 2010 12:13 PM writes...

"Mr. Llewellyn and his colleagues make many of their products with the help of a rotary evaporator—a piece of lab equipment resembling a food processor that heats and evaporates liquid chemicals, turning them into powders."

LOL. This is the worst description of a rotavap I've ever heard. A food processor?

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24. newnickname on November 1, 2010 12:19 PM writes...

Did anybody actually see that TV show "Breaking Bad" that was supposed to be on in 2008? C&EN had a writeup:

CEN, March 3, 2008, 86(9), 32-33.

'Breaking Bad'
Novel TV show features chemist making crystal meth
Jyllian Kemsley

Chemistry is the study of change, lectures Walter White, a high school chemistry teacher in Albuquerque, N.M. Electrons change their energy levels, molecules change their bonds, and elements combine and form into compounds. That's the cycle of chemical life. "It is growth, then decay, then transformation," he says. [...]

Truth is stranger than fiction? (Nah, not so strange.)

Speaking of Darwin Awards, this one only comes close but is, uh, interesting:

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25. Annette on November 1, 2010 12:25 PM writes...

Yeah, "Breaking Bad" is a great show. I haven't noticed any chemistry errors, either. The writers are careful not to reveal too much information about how to synthesize methamphetamine (though I'm guessing aspiring meth cooks wouldn't need a television show anyway).

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26. John on November 1, 2010 1:14 PM writes...

Derek, this is an inexplicably ahistorical post.

I suggest you read the older entries in Walter Sneader's Drug Discovery: A History. The much higher CNS discovery rates of 50-100 years ago are partially attributable to the old chemist's practice of self-dosing.

As mentioned above, Shulgin discovered, synthesized, and bioassayed at least 230 psychoactive compounds by himself, and remains healthy and highly lucid at age 85. In other words, for every MPTP there are at least 230 MPPPs.

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27. Stiv on November 1, 2010 1:26 PM writes...

"Advocates for decriminalized various drugs often make the point that we know what their effects are, and that society would be better off dealing with them than dealing with the effects of trying to suppress the drugs themselves. They may be right, actually - I haven't made up my mind about that one yet"

As you have previously expressed Libertarian leanings, I am very surprised that you are sitting on the fence on this one......

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28. Wonk on November 1, 2010 1:48 PM writes...

@TFox. It isn't regulation that slows down the introduction of NCE's. It is the time-consuming and costly process of demonstrating that they produce clinical benefits and acceptable risks. Were there no regulation, would you not want to do that?

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29. Wonk on November 1, 2010 1:49 PM writes...

@TFox. It isn't regulation that slows down the introduction of NCE's. AT least, it is mostly not the time for regulatory review; it is, rather, the time-consuming and costly process of demonstrating that they produce clinical benefits and acceptable risks. Were there no regulation, would you not want to do that?

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30. coprolite on November 1, 2010 1:51 PM writes...

Yet another comments section that compares Audrey Hepburn to Ron Jeremy.

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31. BFS on November 1, 2010 1:58 PM writes...

“Ms. Whalen and her colleagues make many of their articles with the help of a word processor – a piece of journalistic equipment resembling a xylophone that generates English letters, turning them into words.”

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32. Chris Barts on November 1, 2010 2:49 PM writes...

"There are plenty of chemotypes out there that will drop you right into the CNS receptors."

Well, that's easy, then: Ban everything that uses those chemotypes. For The Children.

(If you are dependent on a drug based on one of those chemotypes, we might allow you to keep using, kind of on the down-low, but gods have mercy on you if you piss someone off because the DEA certainly won't.)

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33. NHR_GUY on November 1, 2010 3:00 PM writes...

Speaking of 'Breaking Bad", on the chemistry side it seems pretty accurate. My one peeve is in the pronunciation of Methylamine. They pronounce it "Meth-La-Mean". For a show that values its authenticity, and even has a chemist in its employ as technical expert, how could they come up with such a screwed up pronunciation. Even the Brits I know don't pronounce it that bad. Though on a side note, my PhD adviser was a Brit and it took me a couple months to figure out what he meant when he said to add "Tri-thy-la-mean" to a reaction.

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34. Annette on November 1, 2010 3:19 PM writes...


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35. Flavor on November 1, 2010 3:32 PM writes...

Every once in a while they find loads of discardeds solvents and active labs here in the Netherlands. Indeed most of the product is for exports, so we have coke coming in and pills going of the country. Those are mainly the normal 'mdma'types blended with other mainstream goods. The market for designer drugs is much smaller IMHO. The other week they showed a rotavap and the 'expert' noted that there were only three of these sophisticated things in the EU. Yeah he said that...on tv

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36. milkshake on November 1, 2010 4:46 PM writes...

Breaking bad: here is a partial list of cringe-worthy chemistry errors that showed the consultants were DEA forensic chemists but not synthetic organikers:
1) reaction of red P with hydroxide in a saucepan that generates huge quantity of PH3 gas enough to gas the whole camper into a gas chamber (and the bad guys choking on it instantly). PH3 is smelly but not irritant and is insidious poison with a delayed action
2) Highschool teacher goes to his supply room and grabs two galon-sized jugs of 48% HF out of four they had on the shelf.
3) with two gallons of 48% HF his buddy manages to dissolve the bathtub and good part of a bad guy plus a hole in the floor - and no one chokes on the fumes. In reality they would need at least half a drum of HF.
4) giant crystals of mercury fulminate passes as crystal meth. Hg fulminate crashes out from nitric acid as a greyish-white muddy precipitate that is not possible to re-dissolve and turn into chunky glass-like rhombs
5) Preparation of phenyl acetone. Why buying a special pyrrolizer with thorium catalyst. A much simplier room-temp procedure uses phenylacetic acid, Ac2O and pyridine.
6) Racemic meth from phenyl acetone being accepted by the gang distributors as a great product: racemic meth does not form beautiful glass-like crystals and has only half the potency of the optically pure material prepared from pseudoephedrine/ephedrine
7) experimental setup and performance in the mobile lab - the overfilled flask with the react mix bubbling high up into reflux condenser

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37. Anonymous on November 1, 2010 8:45 PM writes...

well with all of those unemployed American med chemists out there, you shouldn't be surprised if this also starts happening over here, too.

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38. BCP on November 1, 2010 11:23 PM writes...

The most disturbing aspect of this story to me is the idea of these guys plucking analogues from god knows what journal article and scaling them up (not) for human consumption. Anyone who has spent a decent amount of time in medicinal chemistry has likely seen the capricious nature of preclinical tox signals when you study structurally related species. Morally far worse than your average meth lab hack IMO.

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39. Mr L on November 2, 2010 2:28 AM writes...

The good news is that the guy's apparently mostly talk - if you search around all you come across is complaints about unshipped 'product.' He even ripped off the guy who designed his web site; the fact that he has one implies that he's not doing nearly as much face-to-face business as he can handle.

Also, did anyone notice that his previous business was in, uh, 'construction?' Belgium has the mob, right?

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40. Toxie on November 2, 2010 5:42 AM writes...

This guy seems to be an outright scammer which is probably the best case for his customers. I would be astonished if he operated a lab of any sort - even the major "research chemical" vendors in Europe purchase in bulk from manufacturers in Asia. The internet drug scene is real, however, and has been around long enough to die once and be resurrected:

There are plenty of research chemical enthusiasts who are scientifically-minded in a 19th century sort of way. I don't think it's unreasonable to say that the psychedelic adventures of Alexander Shulgin and his disciples recall the anesthetic self-experimentation of Humphry Davy et al. Since the 4-MMC/Mephedrone explosion in the UK, though, the "industry" has been overrun by scumbags like this (more than it was before, I mean) which endangers ALL recreational drug users.

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41. flavor on November 2, 2010 5:45 AM writes...

yes they have the mob. We call it the EU and all of it associates are wiseguys. But that's an whole other discussion

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42. processchemist on November 2, 2010 6:56 AM writes...

Breaking Bad:

The plant used to scale up the production: improbable reactor design, all stainless steel. If used to make meth hydrochloride, two runs to turn the vessels in useless corroded garbage. And I heard the word "Thorium" used about the hydrogenation catalyst...
(By the way I'm a big fan of the show)

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43. MIMD on November 2, 2010 7:53 AM writes...

How people like this sleep at night is a continuing mystery to me.


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44. Gadfly on November 2, 2010 9:19 AM writes...

Funny how so many people who style themselves liberatarians when taxes are at issue turn into stern, uncompromising paternalists when it comes to vice. Pray tell, Dr. Lowe, how exactly does the use of unsafe recreational drugs by idiots pick your pocket or break your leg? Or is your pose of principled liberatarianism just a cover so you can whine about taxes?

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45. flavor on November 2, 2010 9:21 AM writes...

yes they have the mob. We call it the EU and all of it associates are wiseguys. But that's an whole other discussion

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46. dvizard on November 2, 2010 2:32 PM writes...

Personally, I could care less. Are these "chemists" bad people because they supply the market, which is created by people who deliberately eat stuff of which they know very well that it will most likely mess with their brain? There is no such market without the consumer.

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47. Peter on November 2, 2010 5:09 PM writes...

This is somewhat reminiscent of Alexander Shulgin - with one big difference: He never tried to make a profit from his tremendous discoveries. He is actually a real scientist with good intentions. The impact of his magical half dozen cannot be underestimated. Personally, I think every CNS chemist should experience the action of an appropriate dose of MDMA or 2C-B. This helps to put things into perspective and understand what we organic chemists are capable of.

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48. metaphysician on November 2, 2010 5:38 PM writes...


One can believe it is the right of the individual to take what drugs they wish of their own free will, and also believe it is recklessly immoral to manufacture and sell drugs to others with no idea of their safety.

( Note the fairly recurring comments earlier: "This is why we should legalize, so people can take drugs that actually undergo safety testing." )

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49. Gadfly on November 3, 2010 9:09 AM writes...

@48: There is a difference between calling something immoral or unethical and calling for its abolition. The former is a personal judgement, while the latter is an attempt to inflict that judgment upon others. The former can be entirely consistent with civil liberatarianism, while the latter becomes paternalistic pretty damn quickly.

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50. TFox on November 3, 2010 2:24 PM writes...

For me, I guess the question raised is this: imagine a world where recreational chemicals are generally socially accepted. What would an appropriate regulatory regime look like? You don't need to test efficacy - by definition, the consumer themself can evaluate that. And risk is complicated: usually you balance medical risk vs medical benefit, but the medical benefit for these compounds is zero, and the risk never is, so how does the regulator choose between compounds that are no worse than what the users are taking already, and should be approved, vs compounds that are too toxic even when used as directed, and should be banned? It seems like a hard problem, even in the abstract.

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51. Norepi on November 3, 2010 4:35 PM writes...

I lost it at "ashamed to share a phylum with these people." Very funny. Consider this sort of behavior natural selection.

David Nichols is on my committee. He is one of the most outspoken and most outrageous individuals I have ever had the pleasure of working with.

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52. Anonymous on November 4, 2010 12:34 AM writes...

This made me laugh!
35. Flavor :
"The other week they showed a rotavap and the 'expert' noted that there were only three of these sophisticated things in the EU. Yeah he said that...on tv"
This is amazing - only three!? How on earth do those europeans get anything done when they're all waiting in line to vac their solutions down?
I am perpetually amazed by how little non-chemists know. I mean really? Only three?

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53. Osaka on November 5, 2010 4:35 PM writes...

50: You are over-thinking the issue. On one hand, safety could be easily defined; if the current drug produces the same effect with less side effects, don't replace it. If the newer one has less side effects, replace it as the standard. We could easily classify most drugs as producing certain effects, and then propose a "standard" one for each particular effect. Any new drugs would be measured against the standard, or have to open a new niche in some way. This is quite similar to how drug design is already done! If your SSRI doesn't cause significant benefits over, say, prozak, it is going to need some sort of other niche to get into!

As for efficacy, why not judge efficacy? Just because the user can do it does not mean they SHOULD. Medications must prove safety AND efficacy; otherwise we'd be selling sugar water to everyone for three month jumps at a time (oh wait, or just pure water like homeopathy). Establishing efficacy on some scale would allow consumers to make better choices, and allow fairer competition.

Don't treat lifestyle choice drugs any different than health benefit drugs; they are intrinsically related.

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