Scientist Haunted By Misuse Of Drugs He Invented

by The Associated Press
January 5, 2011

David Nichols studies the way psychedelic drugs act in the brains of rats. But he is
haunted by how humans hijack his work to make street drugs, sometimes causing
overdose deaths.

Nichols makes chemicals roughly similar to ecstasy and LSD that are supposed to help
explain how parts of the brain function. Then he publishes the results for other
scientists, hoping his work one day leads to treatments for depression or Parkinson's
disease.

But Nichols' findings have not stayed in purely scientific circles. They've also been
exploited by black market labs to make cheap and marginally legal recreational
drugs.

"You try to work for something good, and it's subverted in a way," Nichols said. "I try
not to think about it."

Now the 66-year-old chairman of the Purdue University pharmacology department is
speaking out in one of the world's most prestigious scientific journals to describe an
ethical struggle seldom discussed by brain researchers.

"You can't control what people do with what you publish, but yeah, I felt it
personally," he said in a phone interview, explaining that his struggles are probably
somewhat similar to those faced by the inventor of the machine gun, although not as
severe. The journal Nature published his essay online Wednesday.

"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?" Nichols wrote. "That would be a disaster of immense proportions. This
question, which was never part of my research focus, now haunts me."

Nichols has studied psychedelic drugs for more than 40 years, concentrating on
serotonin. That's a basic chemical "that goes to every part of the brain. It's involved
in appetite, sleep, sex, aggression, you name it," Nichols said in the interview with
The Associated Press. "It really plays a key role in brain activation, the difference
between being awake and being asleep."

Nichols estimates that at least five of his compounds — out of hundreds   have been
turned into street drugs.

His drug work used to be a joking matter. People would ask him if he needed human
test subjects, and he would respond: "No, it's just rat stuff."

"I never thought of these getting out of the lab," he told the AP. Sure, the field
includes research into LSD and other hallucinogens, but Nichols never imagined his
work escaping the lab and causing death. The worst would be maybe someone
getting high on stuff they shouldn't, he figured.

"Every time we make a molecule now, I do think, 'Is this the one that's going to be a
problem?' I never used to think that before," Nichols said.

One chemical was so potent that "I just stopped and said, 'We're not going to study
this one. This stuff would hit the market big-time,'" he said.

That was not the case almost 20 years ago, when he developed something similar to
ecstasy, but not nearly as potent. Back then it was a little-known street drug. He
published his study, found little interest from pharmaceutical companies in his
chemical, called MTA, and moved on.

But somebody in the illicit world of drug abuse read his research and synthesized that
drug into tablets for street use. It was eerily called "flatliners." But it really didn't
provide much of a high.

"Flatline implies that you're brain dead," Nichols said. "Why would anyone take it?"

People did. They took too much. Their brains were flooded with serotonin, and they
died. The first time Nichols was told about it, only two people had died.

"I sat in my office and thought. 'Wow, if you shoot somebody with a gun, you know
you killed them, but if technology escapes and someone dies," Nichols said, his voice
trailing off. "You're kind of disconnected from it."

At least five or six people died from that first drug. A second drug, a hallucinogenic
called bromo-dragonfly, has killed two others. It could have been worse because it
was chemically similar to a potent toxin that causes liver cancer, Nichols said.

A story last year in The Wall Street Journal said Nichols' published research is a
favorite for European chemists who make black market street drugs. That hit him
hard, but didn't surprise him. In the past year or so, he's been getting inquiries
about his research from investigators and forensic labs.

Johns Hopkins University behavioral biology professor Roland Griffiths struggles with
the same ethical questions when he studies the chemicals behind hallucinogenic
mushrooms. But Griffiths believes the key to scientific progress is the free exchange
of ideas, saying it's better than no information.

University of Pennsylvania bioethicist Art Caplan said there are times when you can
share too much scientific information — with nuclear weapons, biological weapons
and the like — despite the desire for open research. And this may be one of those
cases given the large black market out there, he said.

Caplan said Nichols' essay "should lead to more careful thinking about the
unintended consequences of scientific advances."
~~~~~~~~~~~~~~~

What it should lead to is the realisation that the fundamental idiocy here is drug prohibition, THAT's what should be "haunting" Nichols and many others.  - THS

~~~~~~~~~~~~~~~~~

Published online 5 January 2011 | Nature 469, 7 (2011) | doi:10.1038/469007a

Column: World View
Legal highs: the dark side of medicinal chemistry

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.
Online 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 published 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: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

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