New tests for ‘legal marijuana,’ ‘bath salts’ and other emerging designer drugs

Posted by Biomechanism 

Marijuana plant

Scientists have reported developing new tests to help cope with a wave of deaths, emergency room visits and other problems from a new genre of designer drugs sold legally in stores and online that mimic the effects of cocaine, ecstasy and marijuana. They spoke at the 242nd National Meeting & Exposition of the American Chemical Society (ACS), being held here this week.

The reports, among more than 7,500 on the ACS agenda, focus on drugs sold as “bath salts,” “plant food,” “incense” and other products with colorful names, such as “Ivory Wave,” “Red Dove” and “legal marijuana.” They provide users with a high, but many have not been made illegal and are undetectable with current drug tests. In one presentation on these “legal highs,” a United Kingdom researcher reported a new method to trace the source of the substances in “bath salts.” In the other, a U.S. researcher discussed the challenges facing law enforcement and policymakers in regulating synthetic versions of marijuana.

Oliver Sutcliffe, PhD, and his collaborators reported the successful use of a method called isotope ratio mass spectrometry (IRMS) to determine who is making bath salts — drugs that can cause euphoria, paranoia, anxiety and hallucinations when snorted, smoked or injected — and which chemical companies supplied the raw materials. He and his co-workers are based at the University of Strathclyde and the James Hutton Institute in the U.K.

“With the new method, we could work backwards and trace the substances back to the starting materials,” said Sutcliffe. IRMS measures the relative amounts of an element’s different forms, or isotopic ratio. “This method was successful because the isotopic ratio of the starting material is transferred like a fingerprint through the synthesis,” he explained.

“Bath salts” first garnered significant media attention in the U.K. in early 2010 and then became a problem in the U.S. These products are not in the supermarket soap aisle — they are sold on the Internet, on the street and in stores that sell drug paraphernalia. They are sold in small individual bags for as low as $20 each to provide a cheap, legal high.

The powders often contain mephedrone, which is a synthetic compound structurally related to methcathinone, which is found in Khat. This plant is illegal in many countries, including the U.K. and the U.S. Usually, that would mean that these compounds (and derivatives thereof) would be illegal in those countries too, but because the bath salts are labelled “not for human consumption,” they get around this restriction and other legislation governing the supply of medicines for human use. However, Florida and Louisiana — two hotspots of abuse of bath salts — specifically banned the substances. U.K. officials banned the import of bath salts, which may lead some in the drug trade to set up clandestine labs on U.K. soil, said Sutcliffe. The new method allows law enforcement to track down these bath salts manufacturers.

In previous work, Sutcliffe developed the first pure reference standard for mephedrone and the first reliable liquid chromatography test for the substance, which could be efficiently run in a typical law enforcement lab. The team is also developing a colour-change test kit for mephedrone, which he estimates may be available by the end of the year.

In another presentation, Robert Lantz, Ph.D., from the Rocky Mountain Instrumental Laboratories, described another high that is legal in most of the U.S. — synthetic cannabinoids marketed as incense, a spice product or “legal marijuana” that give a high similar to marijuana without showing up in conventional drug tests.

“We can detect synthetic cannabinoids with modern analytical chemistry techniques, such as liquid or gas chromatography coupled to mass spectrometry, but these assays are too expensive for the 5,000-10,000 urine samples that most drug testing labs receive daily,” said Lantz. Most labs screen for drugs with less expensive antibody assays, but because the structures of these substances are so dissimilar, different antibodies would likely be required for many of them, driving up the cost of a more comprehensive test.

Synthetic cannabinoid abuse rose sharply in 2010, according to U.S. poison control centres, up to 2,863 compared to only 14 in 2009. About 200 synthetic cannabinoids exist, but the U.S. Drug Enforcement Agency (DEA) banned only five. A handful of states, such as Washington, Georgia and Colorado, refused five, but they are not always the same five that the DEA banned. “The states banned several specific compounds without a particular basis for their choices,” Lantz pointed out.

Colorado recently passed a law banning any substance that binds to a cannabinoid receptor in the human body. “The bill was well-intentioned, but technically, the new law not only covers synthetic cannabinoids but also endocannabinoids, which are naturally occurring substances that the human body produces to regulate many normal processes,” said Lantz.

Unfounded pesticide concerns adversely affect the health of low-income populations

Posted by Biomechanism

The increasingly prevalent notion that expensive organic fruits and vegetables are safer because pesticides — used to protect traditional crops from insects, thus ensuring high crop yields and making them less expensive — are a risk for causing cancer has no good scientific support, an authority on the disease said here today. Such unfounded fears could have the unanticipated consequence of keeping healthful fruits and vegetables from those with low incomes.

Bruce N. Ames, Ph.D., developer of a widely used test for potential carcinogens that bears his name, spoke at the 242nd National Meeting & Exposition of the American Chemical Society (ACS), being held here this week. With more than 7,500 reports on new advances in science and more than 12,000 scientists and others expected in attendance, it will be one of 2011′s largest scientific gatherings.

Ames described his “triage theory,” which explains how the lack of essential vitamins and minerals from fruit and vegetables in the diet of younger people can set the stage for cancer and other diseases later in life. A professor emeritus of biochemistry and molecular biology at the University of California at Berkeley, Ames also is a senior scientist at Children’s Hospital Oakland Research Institute, where he works on healthy aging. He developed the Ames test, which uses bacteria to test whether substances damage the genetic material DNA and, in doing so, have the potential to cause cancer. He has received the U.S. National Medal of Science among many other awards.

In the presentation, Ames said that today’s animal cancer studies unfairly label many substances, including pesticides and other synthetic chemicals, as dangerous to humans. Ames’ and Lois Swirsky Gold’s research indicates that almost all pesticides in the human diet are substances present naturally in plants to protect them from insects.

“Animal cancer tests, which are done at very high doses of synthetic chemicals such as pesticides — the “maximum tolerated dose” (MTD) — are being misinterpreted to mean that minuscule doses in the diet are relevant to human cancer. 99.99 percent of the pesticides we eat are naturally present in plants to protect them from insects and other predators. Over half of all chemicals tested, whether natural or synthetic, are carcinogenic in rodent tests,” Ames said. He thinks this is due to the high dose itself and is not relevant to low doses.

At very low doses, many of these substances are not of concern to humans, he said. For example, a single cup of coffee contains 15-20 of these natural pesticides and chemicals from roasting that test positive in animal cancer tests, but they are present in very low amounts. Human pesticide consumption from fresh food is even less of a concern, according to Ames — the amount of pesticide residues that an average person ingests throughout an entire year is even less than the amount of those “harmful” substances in one cup of coffee. In fact, evidence suggests coffee is protective against cancer in humans.

Unfounded fears about the dangers of pesticide residues on fruit and vegetables may stop many consumers from buying these fresh, healthful foods. In response, some stores sell “organic” foods grown without synthetic pesticides, but these foods are much more expensive and out of the reach of low-income populations. As a result, people — especially those who are poor — may consume fewer fruits and vegetables.

But how does a lack of fresh produce lead to cancer and other aging diseases? That’s where Ames’ triage theory comes in.

In wartime, battlefield doctors with limited supplies and time do a triage, making quick decisions about which injured soldiers to treat. In a similar way, the body makes decisions about how to ration vital nutrients while experiencing an immediate moderate deficiency, but this is often at a cost.

“The theory is that, as a result of recurrent shortages of vitamins and minerals during evolution, natural selection developed a metabolic rebalancing response to shortage,” he said. “Rebalancing favors vitamin- and mineral-dependent proteins needed for short-term survival and reproduction while starving those proteins only required for long-term health.” Ames noted that the theory is strongly supported by recent work (Am J Clin Nutr. DOI: 10.3945/ajcn.2009.27930; FASEB J DOI:10.1096/fj.11-180885; J Nucleic Acids DOI:10.4061/2010/725071).

For example, if a person’s diet is low in calcium — a nutrient essential for many ongoing cellular processes — the body takes it from wherever it can find it — usually the bones. The body doesn’t care about the risk of osteoporosis 30 or 40 years in the future (long-term health) when it is faced with an emergency right now (short-term survival). Thus, insidious or hidden damage happens to organs and DNA whenever a person is lacking vitamins or minerals, and this eventually leads to aging-related diseases, such as dementia, osteoporosis, heart trouble and cancer.

And with today’s obesity epidemic, resulting largely from bad diets that lack healthful foods containing vitamins, minerals and fiber, aging-related diseases are likely to be around for some time to come.

Controlling cells’ environments: A step toward building much-needed tissues and organs

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With stem cells so fickle and indecisive that they make Shakespeare’s Hamlet pale by comparison, scientists today described an advance in encouraging stem cells to make decisions about their fate. The technology for doing so, reported here at the 242nd National Meeting & Exposition of the American Chemical Society (ACS), is an advance toward using stem cells in “regenerative medicine” — to grow from scratch organs for transplants and tissues for treating diseases.

Human embryonic stem cells offer the unique ability to not only renew themselves, but to also differentiate into any one of the more than 200 cell types found in the human body.

“Stem cells have great potential in regenerative medicine, in developing new drugs and in advancing biomedical research,” said Laura L. Kiessling, Ph.D., who presented the report. “To exploit that potential, we need two things: first, reproducible methods to grow human stem cells in the laboratory, and second, the ability to make stem cells grow into heart cells, brain cells or whatever kind of cell. Our technology takes a different approach to both of these problems, and the results are very encouraging.”

Biologically, so-called pluripotent human embryonic stem cells have not made up their minds about what to become. That’s essential because these cells, which are derived from embryos, have the agility to develop into the hundreds of different kinds of cells in a fully-formed human body. But controlling their differentiation has also stood as a major barrier to making the stem cell dream come true and using these all-purpose cells in medicine.

Past approaches to growing and scripting the fate of stem cells have involved adding growth-regulating and other substances to cultures of stem cells growing in the laboratory. These conditions left scientists guessing about exactly what wound up in the stem cells. Kiessling and colleagues are pioneering a new approach that involves using chemically controlled surfaces.

Kiessling previously developed chemically modified plastic and glass surfaces that take much of the guess work out of growing stem cells in laboratory cultures. In the past, scientists grew stem cells on surfaces that contained mouse cells. That left scientists with nagging questions about possible contamination of stem cells with disease-causing animal viruses — a stumbling block for using stem cells in potential medical applications. And that growth system was what scientists term “undefined.” There were variations from batch to batch of mouse cells, and scientists never really knew what the stem cells were coming into contact with and how it might be changing them. The synthetic, chemically-defined, surfaces ended that uncertainty. The approach was inexpensive, simple and a much-needed advance in producing stem cells, Kiessling explained.

With the ability to grow stem cells on the synthetic surfaces under chemically defined, or known, conditions, Kiessling’s group took an additional step in their latest research. It found that chemically defined surfaces can exert control over signaling pathways. “Signaling” is how molecules talk to one another and get things done inside a cell. It’s how an immune cell knows to fight an infection or how a pancreatic cell determines that more insulin is needed in the bloodstream, for example. By controlling how molecules inside a stem cell communicate, researchers could someday in the future nudge them to become one type of cell or tissue over another.

To see whether a new chemically defined surface could change signaling in a pilot experiment, Kiessling tested cancer cells. The research involved use of a signaling substance, transforming growth factor-beta (TGF-beta), which controls a range of activities, from cell growth to self-destruction.

“The new surfaces give scientists much more control over cells, opening up a wide range of possible future applications,” Kiessling explained. Building directly on the results of the pilot study, the surfaces could have applications in wound healing. TGF- beta can help wounds heal, but if it touches healthy skin, inflammation or even a cancerous tumor could develop. “We haven’t done this, but you could imagine a bandage that has a localized concentration of the special peptide surface that would recruit TGF-beta just to the wound site,” said Kiessling.

The surfaces also could make it easier to manufacture organs and tissues in the laboratory someday. “We think that this strategy, with different sets of peptides (building blocks of proteins) bound to the surface, could direct certain human embryonic stem cells on the surface to become one type of cell and other stem cells to become a second cell type, right next to each other. For the tissue engineering involved in growing replacement organs, you need to organize specialized cells in particular ways like this.”