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. 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 the Pediatrics report, Dr. Arshid Mir and colleagues describe literature extending back to 1979 (DOI: 10.3109/15563657909010604) on the increased risk of cardiac disturbances, including myocardial infarction, within the first hour of marijuana use. Increased heart rate is a well-recognized effect of marijuana that is mediated by increased sympathetic nervous system outflow to the heart. This 1976 paper in Circulation describes how the majority of this tachycardia can be prevented by premedication with the non-selective beta-blocker, propranolol. But what about...

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DEA already admits defeat on synthetic marijuana ban?
Mar02

DEA already admits defeat on synthetic marijuana ban?

For those following our most persistent story of the last year or so, you’ve already heard that the US Drug Enforcement Administration declared as controlled substances five synthetic cannabimimetics present in “herbal incense” products such as K2 Spice, Mr. Nice Guy, and Blaze. These compounds include JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol. With respect to our chemistry audience here, I discussed on New Year’s Eve how the DEA has authority to also regulate “analogues” [sic] of compounds that have been assigned to Schedule I of the Controlled Substances Act. This amendment to the act gives the DEA latitude to prosecute the sale, use, and possession of chemical analogs or compounds pharmacologically-similar to those explicitly listed as controlled substances. What authority decides what’s an analog or not is still a mystery to me and was the subject of that post. In anticipation of yesterday’s final rule, synthetic marijuana marketers had already been reformulating their products with compounds not named in this rule but existing among the portfolio of retired Clemson University organic chemist, John W. Huffman – namesake of the JWH compounds. (The compound most commonly cited by readers and commenters at my blogs is JWH-250.). As I understood the DEA’s authority, sale of these products containing apparently still-legal compounds could still potentially be prosecuted. Well, in a story from Minnesota Public Radio, a DEA spokesperson is already apparently admitting defeat in response to retailers who are stocking products free of the five named compounds: [Last Place On Earth shop owner Jim] Carlson said that with about 210 similar chemicals available, the manufacturers will try to keep one step ahead of the government “Unfortunately he is correct,” said Barbara Carreno, a DEA spokeswoman in Washington, who confirmed Tuesday that many suppliers are offering retailers products with new chemicals. “There are many of these substances and we chose five common ones because we don’t have the resources to study all of them.” Hmmm. Really? As we’ve also discussed here, several states including North Carolina have put forth legislation that exhaustively bans potentially hundreds of analogs of synthetic cannabimimetics. While the DEA limited their rule to five, it seems odd to me that they are saying, “Oh well,” when they seem to have the authority to apply the rule to related compounds. After all of the quibbling and delay since the DEA first announced its intention to enact this rule last November, is anyone else confused by this throwing up of...

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NC legislators aim to clean up “bath salt” omission
Feb19

NC legislators aim to clean up “bath salt” omission

Earlier this week, I wrote about on the comprehensive chemistry text in two North Carolina state bills – H12/S9 and H13/S7 – to criminalize distribution, sales, and possession of compounds present in a variety of legal-high, designer drug products. One bill specifically addressed compounds present in synthetic marijuana compounds whose extensive list included those eponymous JWH compounds synthesized in the laboratory of Clemson University Professor Emeritus, John W. Huffman (featured here). The other bill addressed mephedrone (4-methylmethcathinone; 4-MMC) and other structural analogs of this amphetamine and cathinone derivative. However, I noted my surprise at the time at the omission of a compound more commonly associated with so-called bath salt products: MDPV, or methylenedioxypyrovalerone. My neuroscience blogging colleague DrugMonkey also remarked to me of his surprise since most other states deal with MDPV in the same legislation with mephedrone/4-MMC because of their structural similarity. But on Thursday I was tipped off by WRAL-TV Capitol News Bureau Director, Laura Leslie, that a separate bill, Senate Bill 77 (S77), was just filed by State Senator Stan Bingham (R, NC-33) that specifically proposes to criminalize MDPV. Unlike the earlier bills, this one does not appear to currently have a House counterpart so I’m unclear as to how this will be dealt with in the other body. The bill now goes to judiciary committee. The “bath salt” phenomenon began to grab US media attention in late 2010 as state poison control centers began to receive reports of emergency room visits by people using legal high products that were not synthetic marijuana. According to Mark Ryan, Louisiana Poison Control Center Director, these products are sold under such names as Cloud 9, Ivory Wave, Ocean, Charge Plus, White Lightning, Scarface, Hurricane Charlie, Red Dove and White Dove. These currently skirt drug laws by claiming “not for human consumption” or as bath salts, plant food, or insect repellent. As with synthetic marijuana products, an advantage of these drugs is that they can’t be detected by the most common urinary drug screens such as the SAMHSA 5 (Quest Diagnostics example here). These products providing those on probation or otherwise subject to mandatory drug testing with a psychoactive alternative to amphetamines or Ecstasy. TIME Healthland writer, Maia Szalavitz, remarked to me recently of her concern about kids hearing stories about “bath salts” and then trying to smoke Mom’s Calgon. Not a good idea. Trying to do so may indeed, “take me away.” From a neuropharmacology perspective, even less data are available on MDPV than for mephedrone. MDPV is the 3,4-methylenedioxy derivative of pyrovalerone, a compound first synthesized by Heffe in 1964 and investigated in the 1970s in Europe as...

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Strong chemistry in NC bills banning legal highs
Feb12

Strong chemistry in NC bills banning legal highs

On Wednesday, two bills passed unanimously in the North Carolina State Senate that would outlaw synthetic cannabimimetics and mephedrone. These compounds are currently sold as Spice incense (e.g., K2, Black Mamba) or “bath salts” (e.g., Ivory Wave), respectively. (Many thanks to WRAL-TV Capitol Bureau Chief Laura Leslie and fellow blogger DrugMonkey for alerting me to these bills via Twitter.). Legislatively, similar bills have been passed and laws enacted in states and municipalities around the US while a proposed scheduling rule by the federal drug agency, the DEA, languishes in an administrative and legal morass. The synthetic marijuana bill, House Bill 12 (Senate 9) and the mephedrone bill, House Bill 13 (Senate 7), were originally both put forth in the NC House by co-sponsors led by Representative George Cleveland (R, NC-14) of Jacksonville, North Carolina, home to the US Marine base Camp Lejeune. Cleveland himself is a retired, 25-year US Marine. The US military has been far ahead of other state and federal agencies in prohibiting use of these chemicals and associated products. But for readers of this blog, the part of the NC bills that most impressed me was the exhaustive and near-encyclopedia listing of chemicals to be outlawed under the bills. For example, while the DEA has proposed to only regulate five compounds (and implied prohibition of structural analogs), take a gander at this list: The following controlled substances are included in this schedule: (6) Synthetic cannabinoids. – Any material, compound, mixture, or preparation that contains any quantity of the following substances, their salts, isomers (whether optical, positional, or geometric), homologues, and salts of isomers and homologues, unless specifically excepted, whenever the existence of these salts, isomers, homologues, and salts of isomers and homologues is possible within the specific chemical designation: a. Naphthoylindoles. Any compound containing a 3‑(1‑naphthoyl)indole structure with substitution at the nitrogen atom of the indole ring by an alkyl, haloalkyl, alkenyl, cycloalkylmethyl, cycloalkylethyl, 1‑(N‑methyl‑2‑piperidinyl)methyl, or 2‑(4‑morpholinyl)ethyl group, whether or not further substituted in the indole ring to any extent and whether or not substituted in the naphthyl ring to any extent. Some trade or other names: JWH‑015, JWH‑018, JWH‑019, JWH‑073, JWH‑081, JWH‑122, JWH‑200, JWH‑210, JWH‑398, AM‑2201, WIN 55‑212. b. Naphthylmethylindoles. Any compound containing a 1H‑indol‑3‑yl‑(1‑naphthyl)methane structure with substitution at the nitrogen atom of the indole ring by an alkyl, haloalkyl, alkenyl, cycloalkylmethyl, cycloalkylethyl, 1‑(N‑methyl‑2‑piperidinyl)methyl, or 2‑(4‑morpholinyl)ethyl group, whether or not further substituted in the indole ring to any extent and whether or not substituted in the naphthyl ring to any extent. c. Naphthoylpyrroles. Any compound containing a 3‑(1‑naphthoyl)pyrrole structure with substitution at the nitrogen atom of the pyrrole ring by an alkyl, haloalkyl, alkenyl, cycloalkylmethyl, cycloalkylethyl,...

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