What We Talk About When We Talk About Drugs

Some number crunching at bluelight.ru.

A fantastic set of interactive graphics tracking conversational trends in drugs at the chat board bluelight.ru reveals some surprises, to the delight of data journalists everywhere. Virostatiq, a software package authored by Marko Plahuta, was put to the task of analyzing traffic at the drug discussion site. Various kinds of plots are available, with endless variables to permutate. Bear in mind that the data that got crunched dealt with the subject of messages, and cannot be directly correlated with drug use, trends, distributions, etc. But it is a fascinating glimpse at what illegal drug users are talking about, and from that, some inferences can be hazarded.

Plahuta writes:

I thought it would be nice to visualize these drug groups based on what users of harm-reduction forums say, so I analyzed around 1.2 million posts on bluelight.ru and constructed a simple diagram that tells a lot…. My whole database contains posts from 2010 until March 2013. Here’s an analytical tool to better understand what’s going on in the recreational drug community. Time is on horizontal axis, while the proportion of posts mentioning specific drug relative to all posts in that month is on the vertical axis. Play around with interactive chart to discover emerging trends, or simply to behold the wax and wane of specific chemicals as they compete for users’ neurological apparatuses, while their manufacturers are temporarily evading ever stricter analog laws.

The chart above represents a graphic created for Addiction Inbox using the visual data provided by Virostatiq. I have singled out six drugs of abuse for discussion. Bear in mind that the trend lines for common drugs like LSD, Ecstasy, marijuana, and methamphetamine all show much higher usage than the ones I have chosen to chart.

—Mephedrone, arguably the most common “bath salt” stimulant, was mentioned at bluelight.ru a lot during 2010, when it came to the U.S. in a major way. But comments have been tailing off pretty steeply ever since. This suggests that mephedrone was sampled and found wanting by those who knew what drug they were taking. Or it could simply be old news by now, and less of a topic for discussion. But if the graph is suggestive of interest levels in the drug-using community, mephedrone seems to have a PR problem.

—Surprisingly, at least to me, a hallucinogen name 2c-e was one of the most talked-about designer drugs of all. 2c-e is a research chemical similar to mescaline but with a spotty track record. Linked to deaths and hospitalizations in Oklahoma and Minnesota, it isn’t known for certain whether the medical problems were due to the pure drug or contaminants. 2c-e is one of the drugs to come out of Alexander Shulgin’s infamous laboratories, and has been around for 20 years. As Tony O’Neill wrote at The Fix: “All in all, it doesn’t sound like the best bet for a recreational Saturday night at the dance club.” As with mephedrone, 2c-e was less talked bout in the last year of the graph.

—Kratom retained a steady popularity over the full 3-year period. Kratom has always been hovering in the background of the opiate family, but seems to have undergone an unprecedented surge in underground popularity of late. From a tree native to Southeast Asia, and often used as a tea, Kratom is powered by an active ingredient called mitragynine—a substance capable of partially activating the mu- and delta-opioid receptors. Kratom serves as a weak opium, and some opiate enthusiasts swear by it for use as a withdrawal aid.

—One of the popular synthetic cannabis products to come out of the Huffman labs at Clemson University, jwh-018 seems to have pretty much cratered as a topic of discussion among drug cognoscenti. Perhaps some of the news about synthetic cannabis and correlations with serious liver problems has taken the shine off that apple. Or simply the fact that, over the few years that synthetic cannabis has been available, users have learned that they prefer the real thing, drug tests notwithstanding.

—Hydrocodone, otherwise known as Vicodin, may have lost some popularity lately due to the popularity of oxycontin and other new synthetic opiate formulations. This is the drug that may have cost Rush Limbaugh his hearing. As a legitimate pain drug, it suffers in comparison with oxycontin, aka Percodan.

—Ketamine is a major topic of discussion, which makes sense. Lately it has rebounded as a party drug, and also scored highly in clinical testing of its efficacy as a short-acting treatment for depression. Unfortunately, use of the drug has been linked to bladder problems  lately.

Marijuana: The New Generation

  

What’s in that “Spice” packet?

They first turned up in Europe and the U.K.; those neon-colored foil packets labeled “Spice,” sold in small stores and novelty shops, next to the 2 oz. power drinks and the caffeine pills. Unlike the stimulants known as mephedrone or M-Cat, or the several variations on the formula for MDMA—both of which have also been marketed as Spice and “bath salts”—the bulk of the new products in the Spice line were synthetic versions of cannabis.

The new forms of synthetic cannabis tickle the same brain receptors as THC does, and are sometimes capable of producing feelings of well-being, empathy, and euphoria—in other words, pretty much the same effects that draw people to pot. But along the way, users began turning up in the emergency room, something that very rarely happens in the case of smoked marijuana. The symptoms were similar to adverse effects some people experience with marijuana, but greatly exaggerated: extreme anxiety and paranoia, and heart palpitations.

As it turns out, there is a very real difference between smoking Purple Kush and snorting “Banana Cream Nuke” out of a metallic packet. The difference lies in the manner in which the brain’s receptors for cannabinoids are stimulated by the new cannabis compounds. When things goes wrong at the CB1 and CB2 receptors, and the mix isn’t right, the results may not be euphoria, giggles, short-term memory loss, and the munchies, but rather “nausea, anxiety, agitation/panic attacks, tachycardia, paranoid ideation, and hallucinations.” Furthermore, the Spice variants do not contain cannabidiol, a cannabis ingredient that has been shown to reduce anxiety in animal models, and reduces THC-induced anxiety in human volunteers. The authors of a recent study suggest that the “lack of this cannabinoid in Spice drugs may exacerbate the detrimental effects of these herbal mixtures on emotion and sociability.”

What concerned the researchers was that, in addition to reports of cognitive deficits and emotional alterations and gastrointestinal effects, emergency room physicians were reporting wildly elevated heart rates, extremely high blood pressure, chest pains, and fever. Fattore and Fratta report that “two adolescents died in the USA after ingestion of a Spice product called ‘K2,’” one due to a coronary ischemic event, and the other due to suicide. What’s going on?

In a paper for Frontiers in Behavioral Neuroscience called “Beyond THC: the new generation of cannabinoid designer drugs,” Liana Fattore and Walter Fratta of the University Of Cagliari in Monserrato, Italy, identified more than 140 different products marketed as Spice, and laid out the extreme variability found in composition and potency. Like a mutating virus, they came to the U.S., starting in early 2009, a new strain seemingly every week: Spice, K2, Spice Gold, Silver, Arctic Spice, Genie, Dream, and dozens of others, the naming and renaming suggesting nothing so much as the proliferating strains of high-end marijuana: Skunk, Haze, Silver Haze, Amnesia, AK-47. Synthetic marijuana comes mainly from manufacturers in Asia, and second generation chemicals have already been put on a to-be-banned list by the DEA. States have jumped all over the problem with duplicate legislation, despite the fact that experts believe a majority of sales take place over the Internet. A third generation of synthetic cannabis variants, which are sprinkled on an herbal base and meant to be snorted, are openly sold and touted as legal. And they are legal, depending upon which one you buy, and where you buy it. Synthetic cannabis is still readily available, affordably packaged, and right on the shelf, or ready for purchase online—unlike the frequently vague and sometimes shady process of scoring a bag of weed. In the beginning, at least, the new drugs were perceived by youthful users as safer than other drugs.

But the most crucial attribute of Spice and related products is that they are not detectable in urine and blood samples. You can cruise all night on Spice, and test clean the next day at work. The kind of cannabis in Spice doesn’t read out on anybody’s drug tests as marijuana. That requires the presence of THC—and the new synthetics don’t have any.

There are four different categories of chemicals used in the manufacture of “cannabimimetic” drugs. The first and best known is the so-called JWH series of “novel cannabinoids” synthesized by John W. Huffman at Clemson University in the 1980s. The most widely used variant is an extremely potent version known as JWH-018.  While JWH-018 is, chemically speaking, not structurally like THC at all, it snaps onto CB1 and CB2 receptors more fiercely than THC itself. The CP-compounds, the second class of synthetic compounds, were developed back in the 1970s by Pfizer, when that firm was actively engaged in testing cannabis-like compounds for commercial potential, a program they later dropped. The best-known example is CP-47,497. While CP-47,497 lacks the chemical structure of classic cannabinoids, it is anywhere from 3 to 28 times more potent than THC, and shows classic THC-like effects in animal studies. The next group is known as HU-compounds, because they originated at Hebrew University, where much of the early work on the mechanisms of THC took place. The last category consists of chemicals in the family of benzoylindoles, which also show an affinity for cannabinoid receptors.

JWH-018, the most common form of synthetic cannabis, and now widely illegal, is considerably more potent than THC—4 times stronger at the CB1 receptor, and 10 times stronger at the less familiar CB2 receptor. The CB2 receptor seems to have a lot to do with pain perception and inflammation, which is why researchers continue to investigate it. But CB2 receptors contribute only indirectly to the classic marijuana high, which is all about THC’s affinity for CB1 receptors, and the effects of using drugs with a very strong affinity for CB2 receptors is not well documented. And therein might lie the source of the problem—or, as Fattore and Fratta describe it, “the greater prevalence of adverse effects observed with JWH-018-containing products relative to marijuana.” A popular compound of the second kind, HU-210, has frequently been found in herbal mixtures available in the U.S. and U.K. According to the study, “the pharmacological effects of HU-210 in vivo are also exceptionally long lasting, and in animal models it has been shown to negatively affect learning and memory processes as well as sexual behavior.”

That, in a nutshell, is what the kids are smoking these days. But wait, there’s more: Besides synthetic cannabinoids, herbs and vitamins, researchers have found opioids like tramadol, opioid receptor-active compounds like Kratom (Mitragyna speciosa), and oleamide, a fatty acid derivative with psychoactive properties. (A combination of oleamide and JWH-018 has been sold as “Aroma.”) Indentifying which of these active ingredients is part of any particular packet of “legal highs” is further complicated by manufacturers’ tendency to mix the ingredients together with various organic compounds—everything from nicotine to masking agents like vitamin E. In fact, almost anything that might make it more difficult for forensic labs to pry it all apart: alfalfa, comfrey leaf, passionflower, horehound, etc. Banana Cream Nuke, which was purchased in an American smoke shop, and made two young girls very sick, contained 15 varieties of synthetic cannabis—but none of the herbal ingredients actually listed on the label.

Unlike the partial activation of CB1 receptors by THC, which takes place when people smoke marijuana, “synthetic cannabinoids identified so far in Spice products have been shown to act as full agonists with increased potency, thus leading to longer durations of action and an increased likelihood of adverse effects.” When it comes to cannabis, users are far better off smoking the real thing, from a harm reduction standpoint, and staying clear of these unpredictable synthetic substitutes.

Graphics Credit: http://www.cityblends.info/2011/10/beyond-thc.html

Fattore, L., & Fratta, W. (2011). Beyond THC: The New Generation of Cannabinoid Designer Drugs Frontiers in Behavioral Neuroscience, 5 DOI: 10.3389/fnbeh.2011.00060