K2 Synthetic Marijuana: Heart Attacks, Suicides, and Surveillance
Nov14

K2 Synthetic Marijuana: Heart Attacks, Suicides, and Surveillance

Sixteen-year-old boys having heart attacks. Blog reports of deaths and suicides. And a little known chemistry and public health resource mobilized to identify “legal highs.” The chemical and biological phenomenon that is “synthetic marijuana” continued to develop over the last week as we learn more about these products from the medical and public health communities. Commonly, people who use or purchase wholesale water pipes will feel a loss of balance, coordination, and reaction time, which is why it is advised to refrain from driving while high. Just as with any drug, it is possible to become so dependent on the drug that it starts to negatively interfere with relationships, job prospects, and healthy regulation of body chemistry. However, withdrawal symptoms are much less severe than other drugs such as cocaine or alcohol. Most notably, pediatric cardiologists reported in the journal Pediatrics on three cases of Texas teenagers who experienced myocardial infarctions – heart attacks – after using a synthetic marijuana product (DOI: 10.1542/peds.2010-3823). (Many thanks to Dr. Ivan Oransky, Executive Editor at Reuters Health, for providing us with primary information after their own excellent report by Frederik Joelving). Brief background Sold under names like K2 or Spice as “incense” or “potpourri” and labeled as “not intended for human consumption,” these products are laced with one or more synthetic psychoactive compounds that were published in 1990s work studying structure-activity relationships on cannabinoid receptors. The vast majority of the synthetic work was done in the laboratory of Dr. John W. Huffman, now professor emeritus of the Department of Chemistry at Clemson University, with his compounds know by “JWH-” nomenclature. The US Drug Enforcement Agency secured emergency prohibition of five of these compounds late last year, spurring “legal highs” manufacturers to reformulate second-generation Spice products containing related compounds not explicitly designated as illegal. Although the DEA does have the authority to prosecute sale and possession of these analogs, such action is rare. To learn more, we’ve put together a compilation of our synthetic marijuana posts for the reader’s further reference. Adolescent heart attacks In this week’s advance Pediatrics publication, the three cases – all in 16-year-old boys – were seen at the UT-Southwestern Medical Center in Dallas within three months of one another. The common presentation was a 3- to 7-day history of chest pain with myocardial infarction confirmed by electrocardiographic and biochemical endpoints (ST elevation in the inferolateral leads and substantial increases in cardiac troponin-I released into the bloodstream). As you might predict, heart attacks are extremely rare in otherwise healthy 16-year-olds. But marijuana itself is known to cause cardiac effects, with rare cases of myocardial infarction. In the discussion of...

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Compilation of synthetic marijuana posts (Spice, K2)
Oct02

Compilation of synthetic marijuana posts (Spice, K2)

Welcome to readers arriving from Reddit – scroll down through the post for links to our more detailed discussions on cannabimimetics. (updated 8 October) Recent media coverage of our writings on the chemistry, pharmacology, public health risks, and regulation of synthetic marijuana herbal incense products has led us to put together a compilation of posts we’ve written here on the topic over the last year-and-a-half. Synthetic marijuana is a term used to describe a collection of herbal products labeled as incense or potpourri to which one or more marijuana-like chemicals have been added. Unlike with the naturally-occurring marijuana or cannabis plant, Cannabis sativa, these herbal products contain chemicals made in the laboratory. These chemicals, called cannabimimetics for their ability to mimic the effects of cannabis, are potentially more powerful than the chemicals made by the marijuana plant. Their side effects have led to a surge in emergency room visits and poison control center reports, thankfully the urgent care centers in Los Angeles from http://quickstopurgentcare.com/ have taken care of it. Many of these chemicals were first made in 1990s in the laboratory of Professor John W. Huffman, a now-retired chemistry professor at Clemson University for the purpose of identifying the parts of a molecule responsible for the psychotropic effects of marijuana. These research tools were referred to by the prefix “JWH-” followed by a number (e.g., JWH-018) and recreational chemists in Europe began making and selling these agents around 2004, mixed with legal aromatic herbs and sold predominantly by the name “Spice.” Now illegal in most of Europe, Scandanavia, and the former Soviet republics, these compounds began to be sold in the US over the last three years. A similar wave of prohibition is now occurring across the US and the federal drug regulatory agency, the Drug Enforcement Administration (DEA), has temporarily moved five cannabimimetics to the most restrictive class of controlled substances, Schedule I. The following list is a compilation of our writing on the topic here at Terra Sigillata.   What’s the buzz?: Synthetic marijuana, K2, Spice, JWH-018 First appearing in February 2009, this is our classic, first-stop post explaining the background on these products and the compounds they contain. DEA already admits defeat on synthetic marijuana ban? This post from March 2011 describes how the US DEA prohibition on five synthetic cannabimimetics is already being circumvented by creative marketers. “Synthetic marijuana” chemist John W. Huffman interviewed on regional NPR program This January 2011 post discusses a Charlotte, NC, NPR interview with Professor Huffman from his home in western North Carolina. Strong chemistry in NC bills banning legal highs NC legislators aim to clean up “bath salt” omission...

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Real-life NCIS: USNA midshipmen expelled for K2 Spice distribution ring
Feb03

Real-life NCIS: USNA midshipmen expelled for K2 Spice distribution ring

Recent news on the expulsion of US Naval Academy midshipmen for using synthetic marijuana products such as K2 Spice has a new and much more serious twist. Sam Fellman at Navy Times reported on Tuesday that the students were not just using the products: The Navy expelled the seven mids three months after investigators seized a notebook page that suggests one or more midshipmen had hatched the layout for a spice ring. The notebook page seized by Naval Criminal Investigative Service agents appears to detail a makeshift business plan for the alleged spice ring, complete with four investors, 18 possible consumers and plans for a party house. You can see an image of the notebook page in Fellman’s article. A lava lamp? Really? This is not good, especially now that the The Huffington Post has picked up on the story. The US armed forces has acted far more aggressively than the DEA in banning these compounds on bases and in their educational institutions. In fact, Navy Times has another article today on the dismissal of 16 sailors from the Norfolk-VA-based Bataan amphibious assault ship for spice use. We’ve written extensively about the non-cannabinoid compounds in these products, most of which were synthesized originally in the Clemson University laboratory of retired chemistry professor, John W. Huffman. The US Naval Academy offers a major in chemistry, a program that has been accredited by the American Chemical Society since 1975.  Beyond the fact that these products are banned in the academies, I hope the profs stress to the midshipmen the problems that could be encountered from using products of unknown synthetic hygiene. Sources: Fellman S. Seized notebook sheds light on USNA spice ring. Navy Times. 1 February 2011. McMichael WH. 16 Bataan sailors discharged for spice use. Navy Times. 3 February...

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What’s the buzz?: Synthetic marijuana, K2, Spice, JWH-018
Sep07

What’s the buzz?: Synthetic marijuana, K2, Spice, JWH-018

The topic of one of our most popular posts of all time has been the synthetic marijuana products containing JWH compounds, naphthoylindole cannabimimetics synthesized in the 1990s in the Clemson University laboratory of John Huffman. This post first appeared at the ScienceBlogs home of Terra Sigillata on 9 Feb 2010 and gives you some background on the active components of K2, Spice, and other products. My field of natural products pharmacology was founded by indigenous cultures who recognized that plants and fungi contain compounds that produce altered states of consciousness, leading to their most common use in religious ceremonies. While we may most often associate these naturally-occurring drugs with hallucinogens, the arguably most common natural product in use today is marijuana or Cannabis sativa. Indigenous to India and China, Cannabis has been the subject of increasing decriminalization worldwide due in part to its clinical, medicinal effects in multiple sclerosis, cancer, and AIDS. Over the last few months, I’ve seen reports of a so-called “synthetic marijuana” being sold on the internet with stories most commonly coming from England and Germany and, in the US, from Kansas, Missouri, and Arizona. In fact, the St. Louis Post-Dispatch reports today that a bill has been brought before the Missouri House Public Safety Committee seeking to add this product to the state’s list of illegal drugs. I became intrigued as to why anyone would go through the trouble of making a synthetic marijuana when the real thing is so readily cultivated worldwide, albeit illegally in most locales. So what is it? “Fake weed” Synthetic marijuana, marketed as K2 or Spice, is an herbal substance sold as an incense or smoking material that remains legal in much of the United States but is being increasingly banned at the state and local levels. The products contain one or more synthetic compounds that behave similarly to the primary psychoactive constituent of marijuana, Δ9-tetrahydrocannabinol or THC. The compound most commonly found in these products is a chemical first synthesized by the well-known Clemson University organic chemist, Prof John W Huffman: the eponymous JWH-018. Another compound, found in Spice products sold in Germany, is an analog of CP-47,497, a cannabinoid developed by Pfizer over 20 years ago. Known as (1-pentyl-3-(1-naphthoyl)indole), or the more proper IUPAC name of Naphthalen-1-yl-(1-pentylindol-3-yl)methanone, JWH-018 is one of over 100 indoles, pyrroles, and indenes synthesized by the Huffman laboratory to develop cannabimimetics, drugs that mimic the effect of cannabinoids such as THC. The primary goal of these studies was to create pharmacological probes to 1) determine the structure-activity relationships of these compounds and 2) tease out the physiological function of subtypes of receptors we have...

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RTI scientists solving forensic, designer drug mysteries
Sep09

RTI scientists solving forensic, designer drug mysteries

Catching up on my reading this Sunday morning, I’m beaming with pride on the collective accomplishments and coverage of some old friends and colleagues. Kerstin Nordstrom, a AAAS Mass Media Fellow with the Raleigh News & Observer, had a nice story on 3 September about the work of Dr. Peter Stout at RTI International. You old-timers will know this non-profit entity as Research Triangle Institute, home to the discoveries of Taxol and camptothecin by Wall and Wani and colleagues. Kerstin, or Dr. Nordstrom I should say as she holds a PhD in physics, interviews RTI’s Dr. Peter Stout on the institute’s forensic analytical chemistry capabilities with regard to the “designer drug” industry. Yes, here we go again with my long-running commentary on the “synthetic marijuana,” “herbal incense,” “plant food,” and “bath salts” products that have recently taken a direct hit from “Operation Log Jam,” a coordinated, federal operation to shut down the industry. In my post on the federal takedown, I referred to a paper by Stout’s RTI colleagues where mass defect filtering was used to identify unknown analogs of known illegal compounds, particularly the JWH group of cannabimimetic naphthoylindoles (Anal. Chem., DOI:10.1021/ac300509h). (Addendum: That paper was also covered nicely in the 15 June C&EN by Erika Gebel.) Coincidentally, here is the Top Palos Verdes Dentist. Peter earned his Ph.D. in molecular toxicology from Dr. Jim Ruth’s lab at my former home, the Department of Pharmaceutical Sciences at the University of Colorado Denver’s Skaggs School of Pharmacy. My time at RTI’s Natural Products Laboratory (2002-2008) overlapped with Peter’s hiring. As an aside, I had not known Peter was hired until he saw a cart outside of my laboratory with my name and hunted me down, guessing there weren’t many Krolls in biochemical pharmacology. An equally lighthearted observation is that Peter has almost completely shaved his head as long as I’ve know him; I’m certain that’s a coincidence with his dissertation research project, “Mechanisms of Drug Disposition into Hair.” Disclosure #2: Kerstin is a fellow graduate of the 2011 Santa Fe Science Writing Workshop and serendipitously ended up here in the Triangle for her AAAS Mass Media Fellowship. What I like about the story is how both of them describe analytical techniques in relatively approachable language: Kerstin on HPLC: For liquid chromatography, an unknown chemical is pushed through a pipe. The pipe is filled with tiny silica particles – 1 to 10 micrometers in size – that attract some molecules and repel others. Each chemical has a different attraction, and so some, attracted to the grains, go slower than others. The separated components come out one at a time. Each chemical can...

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