David Nichols with chemist blogger Andrea Sella on BBC4 IYC programme

Our beloved C&EN online editor, Rachel Pepling, pointed out to me yesterday an insightful post about David Nichols by University College London chemist, Andrea Sella, at his Solarsaddle’s Blog. You’ll recall that my previous post commented on the Nature commentary by Purdue University distinguished chemist and pharmacologist, David Nichols, as he lamented how some of his synthetic schemes for neuroactive compounds have been adopted by those in the recreational street drug industry. In his post, “Is David Nichols just a wee bit disingenuous?,” Sella discusses how Nichols did not reveal in the commentary his professional relationship with revered “psychedelic” chemist, Alexander “Sasha” Shulgin. I probably don’t have to tell chemists about Shulgin – and that Shulgin’s 1991 book co-authored with his wife, Ann, entitled, PIKHAL: A Chemical Love Story, is the central holy book of drug users wishing to expand their consciousness and explore their mystic relationship with the world and themselves. (PIKHAL stands for Phenethylamines I Have Known and Loved – the Shulgins also wrote another book on tryptamines, TIKHAL.). PIKHAL is part fictionalized autobiography of the couple and part synthesis and personal bioassay descriptions of about 200 psychoactive compounds. Andrea noted that he had been invited onto BBC Radio 4’s Material World program to kick off the International Year of Chemistry and had a discussion with producer Roland Pease about Nichols’ relationship with Shulgin: Roland was intrigued when I said that Nichols had made no reference [in the Nature commentary] to Shulgin’s book because it seemed to me that “synthetic drug makers” would take that as a starting point and it wasn’t clear to me why they should stop there and not follow things up. After all, anyone who can make MDMA is someone who can set up a reflux, make a Grignard reagent, and do a Büchner filtration or two. If so, then they probably have a chemistry degree and that means they can search the chemical literature, which they can do in pretty well any public library. In the evening I flipped through the book, looking at the recipes and reading the odd bit here and there. The next day I got a call from Roland. “Do you realize that they’ve published together?”. Sure enough Shulgin and Nichols have six joint publications. I went back to PIHKAL and looked at the reference section and sure enough there were more than a dozen papers with Nichols as first author. And then I spotted it. Nichols wrote the foreward, finishing with wonderful, inspirational sentence:  “Some day in the future, when it may again be acceptable to use chemical tools to explore the mind , this book will be a...

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David Nichols, legal highs, and the social responsibilities of the scientist
Jan05

David Nichols, legal highs, and the social responsibilities of the scientist

Since we ended last year with a post on legal highs – and who decides which analogs are illegal – we logically begin this year, the International Year of Chemistry, with further discussion of synthetic, psychoactive intoxicants. Today, Nature published an excellent commentary from Dr. David E. Nichols, entitled, “Legal highs: the darker side of medicinal chemistry.” Nichols, a distinguished chair in pharmacology at Purdue University’s College of Pharmacy, reflects on how he is haunted by the deaths that could be tracked back to unintended human use of compounds he and his group have synthesized in the course of legitimate biomedical research. Other scientists whose work has been used for nefarious purposes are likely to share these feelings, both in neuropharmacology and other areas of biological and physical sciences. Even in my area of natural products and dietary supplements, several colleagues and I have had our work co-opted by herbal manufacturers to sell their goods, most often in the form of overinterpreting in vitro data to make false claims for human use. The listing of the full citations of our associated papers – or even investigator photographs – on manufacturer web pages to imply that we academic scientists have supported their product claims. However, the same use of synthetic chemistry publications by chemists skirting federal drug laws is a far more serious issue that Nichols addresses in the Nature commentary. Back in October, we discussed here the views of Nichols on one’s scholarly work in neuropharmacology being adopted by the legal highs industry following a Wall Street Journal article by Jeanne Whalen. In fact, Nichols cites that WSJ article in his Nature commentary where his work was described by a Dutch legal highs entrepreneur: He (David Llewellyn) and his chief chemist get ideas for new drugs by scanning scientific literature. They pay particularly close attention to new papers published by scholars known for researching mind-altering, psychoactive substances. David Nichols, a pharmacologist at Purdue University, has been especially valuable, Mr. Llewellyn says. Through his work studying brain receptors, Dr. Nichols has developed a range of psychoactive substances. His papers give a full description of the drugs he’s using, including their chemical makeup. This provides Llewellyn and others with a roadmap for making the drugs. Our colleague Drugmonkey notes that Nichols is a legend in the study of MDMA, or Ecstasy. In fact, Nichols provided other researchers with experimental quantities of this compound early in its history. The work on this and other compounds that modulate serotonergic and dopaminergic pathways in the brain was driven by trying to investigate novel therapeutics, understand the basis of substance addiction, or understand basic mechanisms of...

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Smiles: 2C-I or not 2C-I?
Oct01

Smiles: 2C-I or not 2C-I?

Designer drugs in the news This is tiring enough for a science writer. I cannot imagine being in law enforcement. The pace at which psychoactive designer drugs are appearing on the street is about as challenging for me as keeping up with dietary supplement companies that adulterate their products with actual prescription drugs (an area I’ve been covering since 2007 but a practice that goes back decades.) This week’s designer drug hullabaloo comes to us courtesy of last week’s frightful murder-suicide by Sons of Anarchy actor, the late Johnny Lewis. ABC News is reporting today that Lewis was reportedly taking “Smiles,” a street name for 2C-I, the phenethylamine hallucinogen first synthesized by Alexander Shulgin. 2C-I is more properly known as 2,5-dimethoxy-4-iodophenethylamine. This structural analog of mescaline (3,4,5-trimethoxyphenylethylamine) was among a litany of designer drugs that was criminalized in the US back in July with the Synthetic Drug Abuse Prevention Act of 2012 (Cheryl Hogue had a nice discussion of the Act, including some quotes from yours truly, in the 27 August 2012 issue of C&EN.). But the psychedelic drug information website, Erowid, is proposing that the effects reported for “Smiles” are more likely due to the compound 25I-NBOMe (or 2C-I-NBOMe): the more complex and much more potent 5-HT2A agonist, 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine. The radiolabelled version of this drug was made, it turns out, by some radiochemistry colleagues down the road at RTI International and characterized by Purdue pharmacologist, David E. Nichols (Bioorg Med Chem 2008;16:6116-6123 DOI:10.1016/j.bmc.2008.04.050. Depending on your institutional access, the DOI may not work so you can view the PDF here through the NIH Public Access Program. Again, here is a case of where a laboratory tool has been co-opted by the recreational drug market, a case that Nichols himself lamented in Nature at the beginning of 2011. Why should the non-chemist or general reader care about this structural gobbledygook? 25I-NBOMe/2C-I-NBOMe is about 20 times more potent than 2C-I in binding those 5-HT2A receptors in the brain, the same ones that mediate the psychedelic effects of old-fashioned hallucinogens such as LSD and mescaline. This means that it takes a very low dose of this chemical — low, sub-milligram doses — to experience rather complex sensory and behavioral effects. Here at Erowid is a user experience after a very high dose reported at 3.75 mg – the individual had previously reported a “very enjoyable night” after taking only 0.75 mg. With an unemotional view of the user’s experience, I find it stunning that the human brain is capable of such complex sensory activity after being tickled with some synthetic molecules. But in the context of the Lewis murder-suicide, one would not...

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2011: The year in blog numbers
Dec31

2011: The year in blog numbers

Well, we’re right about at the end of 2011 and it’s time to thank you find readers for checking in with us throughout the year. We’re slowly rebuilding our momentum here at CENtral Science since moving from ScienceBlogs and were just shy of 90,000 visits for the year. Many of our colleagues get that many each month or week, and a few even each day. Still, we’re very happy that you take time to read here – we consider our readers to be top-quality – brilliant, creative, good-looking, and they even smell good, too! I’ll take 90,000 of you folks any day over millions of other less desirable readers. I can’t resist the temptation to put up our year-end traffic report since I have the data available and I just love data sets. In addition, I find it interesting to see what topics garnered the greatest traffic. Below, I’ve put up the list of posts that received 100 or more views. The homepage is obviously the first because of those who have us saved as a browser bookmark. But, no surprise, our major topic of interest overall was synthetic marijuana and other until-recently-legal high such as “bath salts.” But ranking quite highly were our posts on dietary supplements containing aromatase inhibitors for bodybuilding and the newly-approved natural product analog for multiple sclerosis, fingolimod (Gilenya). Title Views Home page 18,563 DEA already admits defeat on synthetic marijuana ban? 10,400 Flurry of FDA action against aromatase inhibitor supplements 5,970 What’s the buzz?: Synthetic marijuana, K2, Spice, JWH-018 5,373 “Synthetic marijuana” chemist John W. Huffman interviewed on regional NPR program 2,856 iAroma synthetic marijuana and the loss of Max Dobner 2,456 K2 Synthetic Marijuana: Heart Attacks, Suicides, and Surveillance 1,853 Fingolimod (Gilenya; Novartis) for Multiple Sclerosis 1,775 NC legislators aim to clean up “bath salt” omission 1,737 David Nichols, legal highs, and the social responsibilities of the scientist 1,611 Compilation of synthetic marijuana posts 1,510 Mephedrone in the U.S. 1,465 NIH biosketch change as “Kick Me” sign? 1,150 Strong chemistry in NC bills banning legal highs 1,121 Ch-ch-ch-ch, Changes 1,093 Skin-bleaching: got mercury? 909 Who decides what’s an analog of a controlled substance? 843 About David 753 Poppy seed tea can kill you (repost) 752 Mike Kastan to lead Duke Cancer Institute 741 GSK to sell iconic Elion-Hitchings building 675 The Future of Chemistry Jobs – Keep Reading and Commenting 670 Real-life NCIS: USNA midshipmen expelled for K2 Spice distribution ring 617 Synthetic marijuana for pharmacists 587 Racism charged in DePaul chemistry tenure denial 540 #icanhazpdf: Civil disobedience? 533 Norman R. Farnsworth, grandaddy of medicinal plant research, passes at 81 521 Intravenous...

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Terra Sig In the News (Hi, Mom!)
Mar01

Terra Sig In the News (Hi, Mom!)

Apologies for the quick note of narcissism but, hey, Mom will be proud of this. Our continued examination of the legal highs industry brought us attention from the online arms of TIME and Nature Chemistry. First, science writer and author, Maia Szalavitz, wrote last week at TIME Healthland about the bans by US states being placed on synthetic cannabimimetics and stimulants (think Spice herbal incense and bath salts, respectively). Early in our days here at CENtral Science, Maia interviewed us for her article and photogallery on natural products and the unusual origins of drugs. She’s since revisited with us for the legal highs story. I had a chance to meet her in person at the recent ScienceOnline meeting in Research Triangle Park and have been really impressed with her science writing on topics ranging from human relationships to substance abuse treatment myths. Before her time at TIME, she was one of the very few writers of high scientific rigor at The Huffington Post. Keep an eye on her at TIME Healthland and Twitter (@maiasz) as the Charlie Sheen trainwreck unfolds. Szalavitz is also the co-author – with Bruce Perry, MD, PhD – of the 2010 book, Born for Love: Why Empathy Is Essential — and Endangered (Amazon link). Our second mention of the last week just popped up this morning on The Sceptical Chymist, the Nature Chemistry blog run by Associate Editor, Dr Neil Withers – most certainly a fine chap but who I have yet to meet in person. However, one could stretch an association between us: Neil earned his MSc and PhD degrees in chemistry at the University of Durham, the British sister city of my Research Triangle Park area home. For their March Blogroll post, Mind-Altering Blogs, Neil asks, “What responsibilities are borne by the creators of compounds that end up as ‘legal highs’?” The catalyst was a 5th January editorial in Nature Chemistry Nature from Purdue chemist and pharmacologist, Dr David Nichols on the use of his science by recreational chemists and the indirect contribution of this work to loss of human life. Therein, he quotes from two of our posts (1, 2) together with that of Derek Lowe at In The Pipeline, and an excellent BBC radio program (okay, “programme,” Neil) with guest British chemist Andrea Sella. Andrea wrote his own blogpost questioning how Nichols might be “a bit disingenuous” about his concerns given his relationship with chemist, Alexander “Sasha” Shulgin. Slightly off-topic, Neil also refers readers to a lovely series of posts from KJHaxton asking readers to deduce the chemical identity of a common household product. I had the pleasure of meeting Haxton...

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