A worldwide arms race has erupted between inventive street chemists who concoct "legal" highs and government officials who wish to regulate and interdict the proliferation of synthetic cannabis products that can send their users to an emergency room or the morgue.

"Legal" pot with names like Spice, K2, Genie Silver and Yucatan Fire now flies off the shelves as "incense" in head shops, convenience stores and, of course, on the Web. The herbal mixtures are infused with synthetic chemicals that hit the same cellular switches in the brain as tetrahydrocannabinol (THC), the psychoactive component of marijuana.

Although these concoctions are often labeled as being unfit for human consumption, users in the know smoke them for a strong high that can sometimes also produce psychosislike symptoms, rapid heartbeat, seizures, even death. The federal government and many states have enacted laws against the use of some of these drugs, but the problem is growing: During the first eight months of this year, the American Association of Poison Control Centers received calls for 4,421 synthetic pot incidents, a 52 percent increase from the total for all of 2010. And last month, three players from the Louisiana State University Tigers college football team were suspended when they tested positive for the compounds after a random drug screening.

In Arkansas, which passed an emergency order in July 2010 to ban synthetic cannabinoids, officials view the problem as severe enough that they have now deployed a network of federally funded laboratories within their state (in collaboration with state and private laboratories) to keep tabs on the protean ingenuity of street chemists, who reformulate these drugs faster than governments can pass regulations to control them. Each time one is banned, chemists retire to the lab to come up with a new synthetic chemical that, at least for a time, is not illegal and will likely elude drug tests.

In the November issue of Nature Medicine, Jeffrey H. Moran, branch chief for the Public Health Laboratory at the Arkansas Department of Health, authored an opinion article recommending that his state's approach of tapping the analytical chemistry and toxicological capabilities of these labs should serve as an example that might be imitated nationwide. (Scientific American is part of Nature Publishing Group.)

Moran suggests that the Laboratory Response Network, set up by the U.S. Department of Health and Human Services and the U.S. Centers for Disease Control and Prevention after 9/11 to combat chemical and biological terrorist threats, be deployed by other state governments for tracking and developing tests for the nearly 150 synthetic pot products in circulation. In Arkansas state agencies have tapped the resources of these labs to identify the latest versions of synthetic pot products and develop tests to detect them. "Ultimately, the collaborative efforts in Arkansas established both the scientific rationale and political support for legislative action," Moran noted in his article.

In March the Arkansas state legislature passed a law that allowed the state's top public health official to decide, after proper testing but without legislative approval, if new forms of synthetic cannabis should be banned for recreational use. In Moran's view, the labs can also serve another purpose. The pursuit of Spice and kindred intoxicants—and the need for a rapid response in developing new tests to detect them—can serve as a practice run for more dire scenarios. "This gives me a teaching tool for the staff here for terrorist events," Moran said in an interview. "Obviously there are not a lot of real instances of those in the workplace."

These efforts mirror those in European countries, where these drugs first appeared, and where a number of governments have laws on the books to remove legal pot products from head shops and online stores. The European Commission also funded the two-year Psychonaut Web Mapping Project in 2009 to monitor the appearance of newfangled compounds, including Spice and other designer drugs like so-called "bath salts," or MDPV (methylenedioxypyrovalerone) and other chemicals.

Some of the most common synthetic cannabis drugs are a scientific experiment that appears to have escaped from the lab, perhaps through the medium of the open scientific literature. Beginning in the 1980s John W. Huffman, a now retired professor of organic chemistry at Clemson University, published journal articles on compounds inspired by the chemistry of THC. At least some of these molecules turned on the brain’s cannabinoid receptors, cellular docking sites, better than THC itself. Some of the easy-to-manufacture compounds identified in the academic papers appear to have been copied by the street chemists. One of them, JWH-018, is among the most common found in synthetic pot. An ingredient missing from the designer formulations is a molecule present in marijuana called cannabidiol, which dampens the anxiety-enhancing properties of THC. Its absence may explain the severe anxiety produced by some of the synthetic cannabis products, fear so intense that, in one case, it provoked at least one user to commit suicide.

Natural cannabinoids, such as THC, are produced in plants and also in the human body to regulate a number of physiological processes. "These receptors don't exist so that people can smoke marijuana and get high," Huffman wrote in an e-mail to Scientific American. "They play a role in regulating appetite, nausea, mood and inflammation." Huffman cautions strongly against their use. "Their effects in humans have not been studied and they could very well have toxic effects. They absolutely should not be used as recreational drugs."

Users seem to be ignoring Huffman's advice. An article in the September issue of Frontiers in Behavioral Neuroscience observes the presence of a growing Web subculture in which users compare personal experiences with these designer drugs and vote for their favorite smoking blend. Spice Diamond, for instance, emerged as the favorite among 41 smoking mixtures in one contest.

In response to the drugs' proliferation, authorities may be tempted to initiate a forceful crackdown. Huffman warns, though, of unintended consequences. Both academics and pharmaceutical companies continue intensive research on the properties of cannabislike compounds, which play a role in the development of osteoporosis, liver disease and some kinds of cancer. Arkansas allows scientific studies on these chemicals to continue, but Huffman worries that, in some cases, the rules could become too strict. "I am concerned about the impact upon much needed research in this area," he says. Huffman restates the consensus viewpoint of many scientists: Addressing the excesses of the party scene should not upend promising scientific investigations that could lead to new insights into the biology of the cannabinoid system in plants and animals, discoveries that could ultimately produce new pharmaceuticals.

Further Reading

1. On the Perimeter of the Synthetic Cannabinoids. Mind Hacks blog.
1a. Marijuana: The New Generation. Addiction Inbox blog by Dirk Hanson, Nov. 2, 2011.
2. Marijuana-based Drugs: Innovative Therapeutics or Designer Drugs of Abuse? Kathryn A. Seely, Paul L. Prather, Laura P. James and Jeffrey H. Moran, Molecular Intervations, February 2011, Vol. 11, Issue 1, pages 36-51.
3. Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds (Abstract) Sebastian Dresen, et. al. Journal of Mass Spectrometry. Volume 45, Issue 10, , October 2010, pages 1186–1194
4. The Brain’s Own Marijuana. Roger A. Nicoll and Bradley N. Alger | Scientific American. November 22, 2004 (Preview).
5. Synthetic Drug Threats. National Conference of State Legislatures.