Naturally Toxic Crowdsourcing
Jul21

Naturally Toxic Crowdsourcing

Among a typically mad summer of academic activities, I am nervously trying to finish a chapter on naturally-occurring toxins for a drug metabolism book. Indeed, this entire chapter will be a science-based rebuttal to the timeworn but misled statement, "Natural is safe." So far, I've focused on naturally-occurring toxins that are metabolically activated by the liver such as the aflatoxins from Aspergillus spp. and pyrrolizidine alkaloids from a litany of herbal medicines such as comfrey and teas such as Jamaican bush tea made from Senecio. These two classes of compounds are acutely toxic to the liver because they are metabolized to highly-reactive nucleophiles. With long-term exposure, both classes are liver carcinogens. I've also talked a bit about α-amanitin, the RNA polymerase II poision from Amanita phalloides and other Amanita species. Here, I mentioned the treatment of such poisoning with extracts of milk thistle in an intravenous form available in Europe. This 2009 case in California is a great example. But let me ask you: what naturally-occurring toxins would you like to know about? They don't necessarily have to be metabolically activated. Some interesting aspects about their absorption, distribution, or excretion are a plus. For example, I feel compelled to cover E. coli toxins, particularly those due to the recent O104:H4 outbreak, as most recently discussed by Superbug writer, Maryn McKenna. But I want to be sure that I'm not missing anything. The crowdsourced suggestions of the hivemind are greatly appreciated...

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iAroma synthetic marijuana and the loss of Max Dobner
Jul16

iAroma synthetic marijuana and the loss of Max Dobner

If you have not heard about the risks of marginally-legal, synthetic marijuana products, a NBC Today Show piece this week certainly raised national awareness of these products sold online, in convenience stores, and smoke shops. (Note: the video autoplays after clicking the hyperlink.) On June 14 a 19-year-old northern Illinois man named Max Dobner crashed into a two-story home at a high rate of speed. The family living there was out but a baby had been napping an hour earlier in the room where the car entered. According to Paul Biasco at the Daily Herald: Police said Dobner was speeding in a 1999 Chrysler Cirrus east on Mooseheart Road, blew through a stop sign at the T-intersection at Route 31 and was sent airborne when the four-door struck a retaining wall. The vehicle flew about 15 feet in the air over an 80-foot stretch before hitting a tree and then the home, Zies said. “The car hit with such force the motor came dislodged from the vehicle and went in through two more rooms and ended up in a bedroom in the back of the house,” [North Aurora Fire District Capt. Todd] Zies said. “It wiped out four rooms: a living room, bedroom, bathroom and another bedroom on the other side.” This photo gallery at the Daily Herald shows the scene of the accident. Charles Menchaca of the Batavia Patch reported this week that in the intervening month since the accident, a potential reason for this inexplicable single-car accident has emerged: Max's brother reported speaking to him about having smoked a legal "potpourri" product called iAroma about an hour-and-a-half prior to the accident. Search engine hits to one of our introductory posts here and to those of our neuroscience colleague DrugMonkey let us know that many of you are looking for information about these products. Therefore, I thought I'd put together an "explainer" for anyone interested in this topic regardless of whether they have a scientific background. Please let me know if this helps you understand - if anything is unclear, please leave a message in the comments below and I'll follow-up. For more technical information written by us and several of our neuropharmacology research colleagues, scroll to the bottom of this post. Synthetic marijuana: where did it come from? Before I suggest background reading, let's just chat about the basics behind these so-called potpourri or incense products, also known as "legal highs." Many mind-altering substances come from my specialized branch of the study of drug action: natural products pharmacology and pharmacognosy. Natural "products" doesn't refer to retail products but rather chemicals made by plants, mushrooms, microorganisms, and other...

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Skin-bleaching: got mercury?
May27

Skin-bleaching: got mercury?

The Minnesota Health Department yesterday issued a warning that skin-lightening cosmetic products sold in the area contain concentrations of inorganic mercury high enough to warrant their disposal as hazardous chemical waste. Details on the warning can be found in this Star Tribune article by Maura Lerner with intern Alejandra Matos (hurray for summer student interns!). State technicians tested 27 products, including 23 creams and four soaps, and found that 11 had mercury levels ranging from 135 to 33,000 parts per million. Federal law permits only "trace amounts," less than 1 part per million. Ramsey County officials said they became suspicious about the lightening creams when a staffer came across a blog about the mercury dangers. The staffer, who worked with immigrant groups, knew the creams were popular among Somalis and others and thought it was worth checking out, said Zachary Hansen, the county's director of environmental health. Skin-lightening creams are popular in African nations as well as in some Asian cultures. A truly excellent 2008 review from a group of clinical dermatologists at the University of Lagos College of Medicine appeared in the International Journal of Dermatology. The authors present therein some of the reasons why dark-skinned individuals might use such products: Some of these are to look more attractive; to go with existing fashion trend; to treat skin blemishes like acne or melasma; to cleanse or “tone” the face and body; or to satisfy the taste of ones spouse. Although the men also use the products for the above reasons, some of them claimed they use the creams because their wives use them; and some male marketers of female cosmetics and toiletries claim they use the products to advertise their wares. Some of the men are homosexuals. The habit of bleaching the skin is most rampant among commercial sex workers who camouflage their occupation in the clinic data as “fashion designer” because of the opprobium attached to prostitution. It is noteworthy that even some people who are naturally fair in complexion, still use the bleaching creams to “maintain” the light skin color and prevent tanning or blotches from sunlight. Currently, the Minnesota warning has not yet been associated with any illnesses or toxicity events. However, mercury-containing skin-lightening creams have been associated with typical, inorganic mercury nephrotic syndromes as early as this 1972 BMJ report from Nairobi where the disease was most commonly seen in "young sophisticated African women." But the risks associated with these skin-bleaching creams are not only due to mercury. More commonly, these products employ hydroquinone (benzene-1,4-diol). A naturally-occurring antiseptic compound - and carcinogenic hepatotoxin - found in the herbal product, uva ursi or bearberry, hydroquinone...

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Four Loko for Locos
Nov17

Four Loko for Locos

Well, that was fast. After a year-long investigation of pre-made, highly-caffeinated alcoholic beverages, the US FDA today warned four companies to go decaf. The U.S. Food and Drug Administration today warned four companies that the caffeine added to their malt alcoholic beverages is an “unsafe food additive” and said that further action, including seizure of their products, is possible under federal law. The companies receiving Warning Letters and their products are: • Charge Beverages Corp.: Core High Gravity HG, Core High Gravity HG Orange, and Lemon Lime Core Spiked • New Century Brewing Co., LLC: Moonshot • Phusion Projects, LLC (doing business as Drink Four Brewing Co.): Four Loko • United Brands Company Inc.: Joose and Max FDA’s action follows a scientific review by the Agency.  FDA examined the published peer-reviewed literature on the co-consumption of caffeine and alcohol, consulted with experts in the fields of toxicology, neuropharmacology, emergency medicine, and epidemiology, and reviewed information provided by product manufacturers.  FDA also performed its own independent laboratory analysis of these products. “FDA does not find support for the claim that the addition of caffeine to these  alcoholic beverages is ‘generally recognized as safe,’ which is the legal standard,” said Dr. Joshua M. Sharfstein, Principal Deputy Commissioner.  “To the contrary, there is evidence that the combinations of caffeine and alcohol in these products pose a public health concern.” Experts have raised concerns that caffeine can mask some of the sensory cues individuals might normally rely on to determine their level of intoxication.  The FDA said peer-reviewed studies suggest that the consumption of beverages containing added caffeine and alcohol is associated with risky behaviors that may lead to hazardous and life-threatening situations.   That last paragraph was what I focused upon in my post over the weekend that was stimulated by a frontpage Raleigh News & Observer article by higher ed reporter, Eric Ferreri (@campus_notes). Large amounts of caffeine taken with a 23.5 ounce beverage containing 12% (v/v) ethanol deceives the drinker into thinking they are less drunk than their motor skills or blood alcohol concentration would reveal. I’m not one for a nanny state but this is in a nutshell is the threat to public health with highly-caffeinated alcoholic beverages. A couple of my dear Twitter followers were having sport with me today about these products and some asked why FDA is acting on these products but not the practice of mixing vodka and Red Bull or whiskey with coffee. The major reason is that these are prepared food products (I’d also add that Four Loko has four times the caffeine as a typical Red Bull). From the FDA’s Q&A today: Under what authority is...

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Undeclared drugs in herbal and non-botanical dietary supplements
Apr13

Undeclared drugs in herbal and non-botanical dietary supplements

This post appeared originally on 13 April 2009 at the ScienceBlogs home of Terra Sigillata. An interesting question arose the other day when we discussed the Key West acupuncturist who was diverting prescription drugs for personal use as well as in her practice. While we are not certain that the defendant put the cited muscle relaxants and anxiolytics in remedies doled out at her practice, we doubt that the demographic she targeted would be too impressed if she were to hand out prescription drugs. This scenario led our scientific and blogging colleague, DrugMonkey, to ask how common it might be for alternative practitioners to dope their herbs with prescription drugs exhibiting known efficacy. He also notes how disingenuous this practice might be in that the alternative practitioner is admitting in doing so that their herbs and elixirs have no efficacy on their own. I can’t speak to trends among individual practitioners but this practice takes a page from the big boys: the dietary supplement industry. Adulterating commercial herbal products with prescription drugs is so common that the US FDA is keeping a running tally of actions against companies selling supplements containing “undeclared drugs”: the polite regulatory term for deceptive doping of a useless product with a real drug. We’ve spoken about these cases several times before [1, 2, 3, 4, 5, 6]. Most common approaches have been to dope weight-loss supplements with sibutramine, a prescription amphetamine-like, serotonin/norepinephrine reuptake inhibitor sold in the US and Canada as Meridia®. The US FDA list on this class of deception has increased from 28 to 69 products since 22 Dec 2008. For example, we get a large number of hits from readers searching for apple cider vinegar capsules and whether they can help one lose weight – well, yes they can, if they contain sibutramine, of course. Another common adulteration tactic is for erectile dysfunction supplement manufacturers to boost their products with prescription phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil (Viagra®) or related compounds. So popular is this approach that the same manufacturer cited above for sibutramine-adulteration of apple cider vinegar products has also been found guilty of adding PDE5 inhibitors to their “Long Weekend” product. At least their business model is consistent, eh? A recent FDA investigation of such supplements sold online revealed that up to one-third of products are so adulterated. This may all seem like fun and games but there is at least one case in the literature where supplement doping has been associated with unusual cases of prostate cancer (Clin Cancer Res 2008:607-11). In this case, the bodybuilding supplement Teston-6 was found to contain testosterone and other compounds...

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