Legal highs: the dark side of medicinal chemistry

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TommyTooter

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here's something for any ravers in the crowd to think about: :thumbup







davidnichols.jpg

Synthetic chemist David Nichols describes how his research on psychedelic compounds has been abused — with fatal consequences.
David Nichols
This is the start of the international year of chemistry, intended to celebrate the contribution of my field to mankind's well-being. Yet, during the previous year it has become disturbingly clear to me that some of my scientific contributions may not be aiding people's well-being at all. In fact, they could be causing real harm.


A few weeks ago, a colleague sent me a link to an article in the Wall Street Journal. It described a "laboratory-adept European entrepreneur" and his chief chemist, who were mining the scientific literature to find ideas for new designer drugs — dubbed legal highs. I was particularly disturbed to see my name in the article, and that I had "been especially valuable" to their cause. I subsequently received e-mails saying I should stop my research, and that I was an embarrassment to my university.
Chemlogo100.jpgOnline collection.
I have never considered my research to be dangerous, and in fact hoped one day to develop medicines to help people. I have worked for nearly four decades synthesizing and studying drugs that might improve the human condition. One type is designed to alleviate the symptoms of Parkinson's disease, and it works superbly in monkey models of the disease. That same research seeks drugs to improve memory and cognition in patients who have schizophrenia, one of the most devastating human conditions. The other substances I work on are psychedelic agents such as LSD and mescaline. It's in that latter area of research that I have published papers about numerous molecules that probably have psychoactive properties in humans. It seems that many of these are now being manufactured and sold as 'legal highs'.


I first became aware that unknown amateur chemists were watching my papers more than a decade ago. My laboratory was doing research on 3,4-methylenedioxymethamphetamine (MDMA or ecstasy), a project we had started in 1982, before most people had even heard of the drug. We wanted to discover how MDMA worked in the brain because we thought drugs like it might help in psychotherapy. In the process, we studied many molecules that had structures similar to MDMA.



One was 4-methylthioamphetamine, or MTA, which could inhibit the enzyme that breaks down serotonin in the body. Between 1992 and 1997, we published three papers on the effects of MTA in rats, including a study showing that MTA might have potential in the treatment of depression, and could possibly be superior to currently marketed drugs.
“I was stunned. I had punished information that ultimately led to human death.”


Without my knowledge, MTA was synthesized by others and made into tablets called, appropriately enough, 'flatliners'. Some people who took them died. Now, any knowledgeable person who had carefully read our papers might have realized the danger of ingesting MTA. It not only caused the release of serotonin from neurons, but also prevented the breakdown of this neurotransmitter, potentially leading to a dangerous serotonin syndrome that can sometimes prove fatal.


My laboratory had shown that rats perceived the effects of MTA as being like those of ecstasy. It seemed that that was the sole motivation for its illicit production and distribution to humans. I was stunned by this revelation, and it left me with a hollow and depressed feeling for some time.



By 2002, six deaths had been associated with the use of MTA. It did not help that I knew some of these fatalities were associated with the use of multiple drugs, or had involved very large doses of MTA. I had published information that ultimately led to human death.


There really is no way to change the way we publish things, although in one case we did decide not to study or publish on a molecule we knew to be very toxic. I guess you could call that self-censure. Although some of my results have been, shall we say, abused, one cannot know where research ultimately will lead. I strive to find positive things, and when my research is used for negative ends it upsets me.


Over the past year or so, I have begun to get more e-mails asking questions about the human effects of other materials that my laboratory had studied. Forensic laboratories began to send me requests for samples of drugs that they suspected were appearing on the black market, but which were so new that there are no analytical standards. Thankfully, most of the other molecules we have published on could not kill, at least not at reasonable dosages. But at very high doses, or mixed with other substances, they could become part of a lethal mix.


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.



David Nichols is the Robert C. and Charlotte P. Anderson Distinguished Chair of Pharmacology at Purdue University in West Lafayette, Indiana. e-mail: drdave@purdue.edu
 
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edgray

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MTA would be illegal in the UK by default, it's a member of the amphetamine family, and drug scheduling over here is done by category. I think in Spain too.

Interesting, I don't think the guy should feel bad though, he didn't put the drug into people's mouths, they took it of their own volition.

Interestingly, MDMA was determined to be the safest illicit drug by former UK drug advisor David Nutt.
 

Peter Parka

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Yawn! More scaremongering about drugs. Maybe if they stopped banning them, people wouldn't keep coming up with new ones. Its like all that fuss about miow miow last year. Oh, there were a couple of deaths which couldn't be directly blamed on the drug, more likely the people were pissed out of their nut when they did it. No one's calling for alcohol to be banned despite it being far more dangerous. And even if I do a drug and die, I'm an adult and I knew the risks. BTW, I like miow miow, it's probably my favorite drug, never had any bad effects off it either but them I just take a couple of little lines and maybe a tiny bit more hours later when it's worn off and I just take it every now and then, not regularly. It's people going stupid on drugs who put themselves at the most risk.
 

edgray

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Yawn! More scaremongering about drugs. Maybe if they stopped banning them, people wouldn't keep coming up with new ones. Its like all that fuss about miow miow last year. Oh, there were a couple of deaths which couldn't be directly blamed on the drug, more likely the people were pissed out of their nut when they did it. No one's calling for alcohol to be banned despite it being far more dangerous. And even if I do a drug and die, I'm an adult and I knew the risks. BTW, I like miow miow, it's probably my favorite drug, never had any bad effects off it either but them I just take a couple of little lines and maybe a tiny bit more hours later when it's worn off and I just take it every now and then, not regularly. It's people going stupid on drugs who put themselves at the most risk.

Is that miaow miaow any good then? what are the effects of that?
 

Peter Parka

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Is that miaow miaow any good then? what are the effects of that?

I like it.I'd rather do it than coke. It's a bit harsher going up the nose but your nose dosent go numb like with coke, you just get a nice mild warm feeling in it. As for the effect, it keeps you alert and talkative like coke and speed yet you dont talk a load of shit like you do on those drugs. You also get a nice mellow feeling of happiness at the same time. The effects are good too because you peak within the first 5 minutes but stay on that level for about 3 - 5 hours. Like I say, I'll have two little lines before going out and that will keep me going most of the night.:thumbup
 

edgray

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I like it.I'd rather do it than coke. It's a bit harsher going up the nose but your nose dosent go numb like with coke, you just get a nice mild warm feeling in it. As for the effect, it keeps you alert and talkative like coke and speed yet you dont talk a load of shit like you do on those drugs. You also get a nice mellow feeling of happiness at the same time. The effects are good too because you peak within the first 5 minutes but stay on that level for about 3 - 5 hours. Like I say, I'll have two little lines before going out and that will keep me going most of the night.:thumbup

Can you send me some to Spain? I don't think you can get it here, I'd like to try it, so bored of coke... plus its too damn expensive for me...
 

Peter Parka

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It's illegal here now too, thanks to the Sun bringing it to everyones attention and scaremongering about it so sending it in the post is probably quite stupid. The funny thing is, it's got a lot more popular since it was banned. The war on drugs is obviously working well the way it is.:sarcasm
 

edgray

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It's illegal here now too, thanks to the Sun bringing it to everyones attention and scaremongering about it so sending it in the post is probably quite stupid. The funny thing is, it's got a lot more popular since it was banned. The war on drugs is obviously working well the way it is.:sarcasm

ha, how utterly predictable. Politicians must be the stupidest people on the planet. Either that, or just plain insane.

A good definition of insanity: trying the same thing over and over expecting different results.
 

TommyTooter

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peter, i don't think this was scare mongering. i forgot to include the source but it wasn't mainstream media by any stretch. it's a statement of shock by the primary researcher and patent holder on a process that is being pirated and marketed in an inflated black market economy with overdose deaths associated with his work.

i personally don't use designer drugs. i like mine to grow in the ground. smoke or toot a little coke or heroin once in a while but don't put any laboratory powders up my nose. i'm very allergic and don't want to take any chances. codeine almost killed me with anaphylaxis.

that is exactly the worry that nichols had about his inventions being distributed on a black market. there's no quality control and the drugs are not being prescribed or monitored by a responsible physician.

the legality and drug war issues are really peripheral to the main thrust of the article.
 
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