In the American comedy drama Breaking Bad impoverished school chemistry teacher, Walter White, is diagnosed with terminal lung cancer, discovers his wife is newly pregnant and is increasingly estranged from his teenage son, Walt Junior, who now prefers to be called Flynn. Walter knows meager family savings will not cover treatment costs. But, a chance meeting with a former student turned crystal meth dealer, Jesse Pinkman, leads to Walt’s previously unrewarded chemical skills turning out highly profitable high quality crystal meth.
Breaking Bad is fascinating fiction, but criminal chemists do exist and are increasingly trawling the scientific literature for inspiration and legal workarounds. There are countless “legal highs” on the black-market exploiting loopholes in the law that is slow to respond to new compounds hitting the streets. Miaow miaow (mephedrone), a synthetic derivative of the active component in the east African khat plant, for instance, was sold surreptitiously as plant food. It was ultimately banned but other entirely synthetic compounds labeled as “legal highs” are emerging all the time, causing the usual tabloid hysteria and political knee jerking.
There are many cultural and social issues that date back millennia that have led many people to equate chemistry with happiness. However, the current fashion for legal, herbal highs has many scientists worried. In a recent issue of the journal Nature (Nature 469, 7 (2011) DOI: 10.1038/469007a), David Nichols, a professor of pharmacology at Purdue University in West Lafayette, Indiana, described how his research into psychedelic compounds has been abused, sometimes with fatal consequences. Nichols investigates these compounds as part of research into Parkinson’s and other diseases, but criminal chemists in Europe have been taking inspiration from his findings.
Back in the 1980s, Nichols was working on a little known compound called 3,4-methylenedioxymethamphetamine, or MDMA, which goes by the non-chemical name of ecstasy. At the time, few people knew of this compound’s effects on the brain and fewer still had ever used it as a drug of abuse. Nichols had hoped that MDMA might be useful in psychotherapy. By the 1990s, when Ecstasy was well known and well used, Nichols team were working on 4-methylthioamphetamine, or MTA, which apparently had antidepressant activity through its powerful ability to release serotonin in the brain. Unknown to Nichols, word had reached the criminal chemists and illicit MTA tablets became the street drug known as “Flatliners”. The lethal hyperthermia and organ failure caused by this substance precluded it from further pharmacological development, but did lead to several reported deaths among abusers.
If Nichols is inadvertently lending inspiration to criminal chemists, then organic chemist John W. Huffman of Clemson University, South Carolina, is the unwitting creator of herbal high chemistry. Huffman has synthesized more than 450 novel compounds during more than a quarter of a century in science. One of those compounds, known as JWH-018, first constructed in the late 1990s has marijuana-like effects. It, and the relatively simple synthetic schemes used to make it were hijacked by criminal chemicals and the innocuous-sounding JWH-018 became “Spice” when it hit the streets.The chemistry Huffman works on is aimed at understanding the brain’s cannabinoid receptors and the development of novel drugs for treating nausea, glaucoma and appetite problems, without the “high”. JWH-133 hits the cannabinoid receptor, CB2, but does not produce a high. Ironically, he has expressed bemusement at how JWH-018, which was never meant to be smoked, has become so popular as a synthetic cannabis as no one has tested its safety clinically.
Any scientific research in this area will inevitably draw the attention of those seeking illicit access to drugs. Chemists and others might worry that their synthetic schemes are simply opening up routes to yet more drugs of abuse. However, the research is too important for legitimate work to be stifled. Instead, there is a need to raise awareness of the potentially lethal effects of inhaling, ingesting, or imbibing chemicals of unknown toxicity. That said, in a world where people often do equate chemistry with happiness there is little chance that such a campaign would have any significant impact.