Know Your Powders

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.

Review: Memoirs of an Addicted Brain

“I’m a drug addict turned neuroscientist.”

What’s it like to swallow 400 milligrams of dextromethorphan hydrobromide, better known as Romilar cough syrup? “Flashes of perception go by like clumps of scenery on either side, while you float along with the slow, irresistible momentum of a dream.” Marc Lewis, a former addict, now a practicing neuroscientist, further muses: “But what was Romilar? It sounded like an ancient kingdom. Would this dark elixir take me to some faraway place? Would it take me into another land? Would it be hard to come back?”

In Memoirs of an Addicted Brain: A Neuroscientist Examines his Former Life on Drugs, Dr. Marc Lewis follows his description of his gateway Romilar drug experience with the neurological basics of the matter: “The problem is that the NMDA receptors in my brain are now clogged with dextromethorphan molecules! The glutamate isn’t getting through. The receptor neurons aren’t firing, or they’re not firing fast enough…. Drugs like DM, ketamine, PCP, angel dust, and those most damaging of substances, glue and gasoline, are called dissociatives, because they do exactly what drugs are supposed to do: they dissociate feeling from reality, meaning from sense—and that’s all they do.”

Speaking of the self-reinforcing cycle “through which calamities of the mind arise from vulnerabilities of the brain,” Lewis argues that dissociatives only produce an absence. As a friend of his puts it with regard to another popular dissociative, “Nitrous oxide doesn’t give you consciousness. It takes it away.” And then, the friend adds: “Just bonk yourself on the head with a baseball bat if you want to lose consciousness.”

Lewis ultimately turns to opioids. “The emotional circuitry of the ventral striatum seems to derive its power from an intimate discourse between opioid liking and dopamine wanting.” In the end, this partnership does more than produce pleasure. It also, Lewis points out, “gets us to work for things.” And by doing that, addictive drugs demonstrate “the fundamental chemistry of learning which really means learning what feels good and how to get more of it. Yet there’s a downside: the slippery slope, the repetition compulsion, that constitutes addiction. In other words, addiction may be a form of learning gone bad. For me, this neurochemical sleight of hand promises much more pain than pleasure in the years to come.”

Lewis does a good job of capturing the feeling of existential despair brought on by uncontrolled addiction: “Contemptible. That’s what I was. Unbelievably stupid, unbelievably irresponsible: selfish, selfish, selfish! But that wasn’t quite it. What described me, what this inner voice accused me of, wasn’t exactly selfish, not exactly weak, but some meridian of self-blame that included both, and also, dirty, disgusting… maybe just BAD.”

How did heroin feel? “I feel relief from that pervasive hiss of wrongness. Every emotional wound, every bruise, every ache in my psyche, the background noise of angst itself, is soaked with a balm of unbelievable potency. There is a ringing stillness. The sense of impending harm, of danger, of attack, both from within and without, is washed away.”

And Lewis provides a memorable summation of the reward system, as dopamine streams from the ventral tegmental area to its targets, “the ventral striatum, where behavior is charged, focused, and released; the orbitofrontal cortex, where it infuses cells devoted to the value of this drug; and the amygdala, whose synapses provide a meeting place for the two most important components of associative memory, imagery and emotion.” In fact, “dopamine-powered desperation can change the brain forever, because its message of intense wanting narrows the field of synaptic change, focusing it like a powerful microscope on one particular reward. Whether in the service of food or heroin, love or gambling, dopamine forms a rut, a line of footprints in the neural flesh.”

And, of course, Lewis relapses, and eventually ends his addictive years in an amphetamine-induced psychosis, committing serial burglaries to fund his habit. “You’d think that getting busted, put on probation, kicked out of graduate school, and enduring a kind of infamy that was agonizing to experience and difficult to hide—all of that, an the need to start life over again—would be enough to get me to stop. It wasn’t.”

Not then, anyway. But Lewis has been clean now for 30 years. “Nobody likes an addict,” he writes. “Not even other addicts.”

If drugs are such feel-good engines, what goes wrong? Something big. “Because when drugs (or booze, sex, or gambling) are nowhere to be found, when the horizon is empty of their promise, the humming motor of the orbitofrontal cortex sputters to a halt. Orbitofrontal cells go dormant and dopamine just stops. Like a religious fundamentalist, the addict’s brain has only two stable states: rapture and disinterest. Addictive drugs convert the brain to recognize only one face of God, to thrill to only one suitor.”  The addict’s world narrows. Dopamine becomes “specialized, stilted, inaccessible through the ordinary pleasures and pursuits of life, but gushing suddenly when anything associated with the drug comes into awareness…. I wish this were just an exercise in biological reductionism, or neuro-scientific chauvinism, but it’s not. It’s the way things really work.”

Photo Credit: http://ebookstore.sony.com/

Tracking Synthetic Highs

UN office monitors designer drug trade.

Produced by the United Nations Office on Drugs and Crime (UNODC), the Global SMART Update  (PDF) for October provides interim reports of emerging trends in synthetic drug use. The report does not concern itself with cocaine, heroin, marijuana, alcohol, or tobacco. “Unlike plant-based drugs,” says the report, “synthetic drugs are quickly evolving with new designer drugs appearing on the market each year.” The update deals primarily with amphetamine-type stimulants, but also includes newer designer drugs such as mephedrone, atypical synthetics like ketamine, synthetic opioids like fentanyl, and old standbys like LSD.

I have summarized some of the findings below:

The first methamphetamine lab in 15 years has been discovered in Japan. Japanese law enforcement seized a suspected residential methamphetamine laboratory outside of Tokyo, the first such seizure since 1995. Two Iranian nationals were arrested. Given the continuously high price of imported crystalline methamphetamine in Japan, there is an increased likelihood that more domestic manufacturers could emerge.

Record ketamine seizures and use has been reported by Taiwan province of China. The FDA reports that ketamine seizures in the first five months of 2010 alone totaled 1465 KG, nearly 300 KG more than last year. Concurrent increases in use were also noted.

The first methamphetamine laboratory in Turkey was discovered. Local media reported the seizure of the lab, in the southern part of the country. The facility reportedly planned to manufacture 100,000 tablets for retail sale at USD 13.40 apiece. In 2009, Turkey reported its first seizures of methamphetamine totaling 103 KG at Istanbul’s airport, which has become a transit point for methamphetamine traffic from Iran to markets in East Asia.

Law enforcement faces unique challenges when dealing with synthetic drug analogs. Customs officers at Prague’s Ruzyne airport reported arresting a Polish national for transporting a substance initially testing positive for ephedrone, a controlled synthetic stimulant. Confirmatory tests, however, revealed the substance to be mephedrone, an analogue not under international control. The event illustrates the challenges law enforcement face when encountering new synthetic substances not under national or international control.

Amphetamine breathalyzer tests may soon be possible, say Swedish researchers. The June issue of the Journal of Analytical Toxicology report reported that the first breath test for methamphetamine and amphetamine detection was successfully conducted in Sweden. Drugs in the exhaled breath are captured in a filter and analyzed using a combination of liquid chromatography and mass spectrometry. Experimental trials on amphetamine-dependent patients admitted to hospital urgency rooms for overdose provided the same results as traditional drug tests.

The U.S. is expanding controls on precursor chemicals for fentanyl and LSD. The Drug Enforcement Administration (DEA) has designated a compound called ANPP as a precursor chemical for fentanyl, an extremely potent synthetic analgesic. Earlier this year, the DEA proposed new controls over ergocristine, a chemical precursor sometimes used in the manufacture of LSD. Clandestine laboratories in the United States employ it as a substitute for ergotamine and ergometrine, both of which are already under international control.

The U.S. indicts 15 people in one of the largest MDMA busts ever. The U.S. Department of Justice announced that a federal grand jury indicted 15 men linked to one of the country's largest ecstasy manufacturing and trafficking rings. Two storage facilities were also seized during the investigation, yielding about 710,000 MDMA tablets. Law enforcement authorities seized more than 1.1 million tablets in all. Authorities believe that the group had been responsible for the distribution of hundreds of thousands of MDMA tablets each month.

Belize stops large shipments of methamphetamine precursors bound for Mexico. Customs authorities in Belize reportedly stopped two large shipments of phenylacetic acid (PAA), or roughly 46 metric tons. Phenylacetic acid can be used in the manufacture of methamphetamine. Reports suggest the chemical came from China and was ultimately destined for Mexico.

Graphics Credit: http://www.unodc.org/

Does Ketamine Cause Bladder Damage?

Special K and Cystitis.

Normally, Addiction Inbox steers clear of alarmist stories about drug use. A lifetime of wildly overstated verbiage about “false drugs,” as the Firesign Theatre comedy group once delightfully phrased it, has left me wary of drug scare stories. Even obvious cases, like Fetal Alcohol Spectrum Disorder and crack babies, are more nuanced problems than most coverage has alleged.

For years now, rumors about bladder problems in recreational users of ketamine have periodically surfaced. These stories go all the way back to the adventures of Dr. John Lilly, famous for dolphin research, as well as sensory deprivation experiments with LSD, ketamine, and other drugs (wildly overdramatized in the movie, “Altered States”). According to hipster lore, Lilly went through a long period of hourly ketamine ingestion in the 1970s, and ended his days in adult diapers, having lost control of his bladder due to ketamine damage.

To the best of my knowledge, this story has never been officially confirmed. But in the last two years, research has surfaced that tends to bolster the Lilly anecdote. What is disturbing is that today, unlike 40 years ago, ketamine has become a fairly common party drug among young users. The drug technically produces a state of “dissociative anesthesia.”  Treated like a hallucinogen, ketamine was originally a tranquilizer used in veterinary medicine. In 1970, the FDA approved the use of ketamine for humans for the maintenance of anesthesia.

The journey from horse tranquilizer to party drug has eluded drug researchers until quite recently. However, in early 2008, researchers sat up and took notice of a report published in BJU International, a urology journal. “The destruction of the lower urinary tract by ketamine abuse: a new syndrome?”

The report details the discovery by physicians in Hong Kong of 59 ketamine abusers who had been admitted to urology units in local hospitals from 2000 to 2007. Interstitial cystitis, also known as painful bladder syndrome, can vary from mild to severe, and its cause is often not known.  Symptoms include painful, frequent, or urgent urination. The researchers found that 71 % of the patients “showed various degrees of epithelial inflammation similar to that seen in chronic interstitial cystitis. All of 12 available bladder biopsies had histological features resembling those of interstitial cystitis.”

The authors conclude that “secondary renal damage can occur in severe cases, which might be irreversible, rendering patients dependent on dialysis.”

Scary stuff. If this were the only study available, it would be tempting to question the results. As it turns out, the Hong Kong study was neither the first nor the last. What is believed to be the first official report of the problem appeared in 2007 in Urology, documenting the case of nine Canadian ketamine users with bladder complications. The authors, affiliated with the University of Toronto, conclude: “As illicit ketamine becomes more easily available, ulcerative cystitis and potential long-term bladder sequelae related to its use may be a more prevalent problem confronting urologists.”

This year, similar reports from Bristol in the UK were published in Clinical Radiology. Researchers with the National Health Service and the Bristol Royal Infirmary discovered “a series of 23 patients, all with a history of ketamine abuse, who presented with severe lower urinary tract symptoms.”  Various imaging techniques revealed smaller bladder volume, bladder wall thickening, inflammation, urethral strictures, and other bladder pathologies. The patients all reported symptoms similar to those reported by the earlier Hong Kong ketamine users.

The report concludes that “many users are well aware, but are often not forthcoming with this information.” They also maintain that “the key to the effective management of ketamine-induced bladder pathology is early diagnosis.”

 Frequent recreational use of ketamine appears ill advised until more research can confirm the true scope of the problem.

Chu, P., Ma, W., Wong, S., Chu, R., Cheng, C., Wong, S., Tse, J., Lau, F., Yiu, M., & Man, C. (2008). The destruction of the lower urinary tract by ketamine abuse: a new syndrome? BJU International, 102 (11), 1616-1622 DOI: 10.1111/j.1464-410X.2008.07920.x

Mason K, Cottrell AM, Corrigan AG, Gillatt DA, & Mitchelmore AE (2010). Ketamine-associated lower urinary tract destruction: a new radiological challenge. Clinical radiology, 65 (10), 795-800 PMID: 20797465

Graphics Credit: http://theintelhub.com/

Psychedelics Back in the Spotlight

But will it be any different this time?

Two papers on the use of psychedelics for the treatment of mood disorders surfaced last week in the prestigious journals Science and Nature. The articles have garnered a great deal of publicity, especially the results having to do with the effect of ketamine on depression. I cannot pretend to offer more insightful coverage than the posts and articles listed below have already done, but I do think it’s profitable to take a closer look at the Nature piece by Franz X. Vollenweider and Michael Kometer. This paper looked at both dissociative anesthetics, like PCP and ketamine, AND “classical hallucinogens,” like psilocybin and LSD.

Traditionally, LSD has been thought of as a relentlessly serotonin-active drug, while ketamine was more actively involved with NMDA and other glutamate receptors. There is accumulating evidence, the researchers believe, that a common mechanism undergirds the operations of both kinds of psychedelics. “Despite their different primary modes of action,” they write, “classical hallucinogens and dissociative anesthetics both modulate glutamatergic neurotransmission in the prefrontal-limbic circuitry that is implicated in the pathophysiology of mood disorders.”

It’s worth noting that Vollenweider and Kometer maintain that almost all depressed patients relapse within two weeks after a single dose of ketamine. In studies of patients with advanced cancer, say the authors, psilocybin improves mood just as effectively, and lasts longer, than ketamine.

While there are significant differences between the subjective effects of ketamine and LSD, there is also “a set of overlapping psychological experiences.” The two trips are different, but not completely different—they share effects such as distortion of perception, visual and auditory hallucinations, a sense that the boundaries of self have softened, and often an ecstatic experience or sense of profound unity. The serotonin-glutamate connection leads the authors to assert that “classical hallucinogens are potent modulators of prefrontal network activity that involves a complex interaction between the serotonin and glutamate systems in prefrontal circuits.”

Alternately, these drugs can trigger a classic “bad trip” in certain users--time, place, circumstance, and innate biology depending.  As the authors put it: “The same hallucinogen might produce a pleasurable loss of ego boundaries combined with feelings of oneness or might lead to a more psychotic ego dissolution that involves fear and paranoid ideation.”

And there you have it: In the case of psychedelics, there are certain extenuating factors which may forever limit the use of these substances for therapeutic purposes. The primary problem is that the drugs are clinically unreliable. With psychedelics, it is always, in a sense, the Lady or the Tiger.  “The strongly dissociative effects of ketamine may limit clinical use despite its reported efficacy,” the researchers conclude. Which is, I think, putting it mildly--and which brings the authors to suggest that pharmacology-assisted psychotherapy might require some tweaks.

Specifically, the hunt is now on for psychedelics that are, well, less psychedelic. In the same way that pharmacologists seek to dial down the euphoric effects of pain medication to lessen the chances for black market abuse, researchers are now looking for ways to tone down the mental fireworks often associated with the use of ketamine, LSD, or psilocybin, on the assumption that these represent nothing but unwanted side effects, rather than the core of the experience that alleviates depression, OCD, and addiction—at least for awhile. These drugs are among the most powerful mind-altering compounds on the planet. So good luck with that project. Studying the behavioral effects of these drugs in the first place is a bit like trying to pin down a writhing fire hose with a pair of tweezers.

Curing or successfully treating chronic ailments like depression and addiction with a power psychoactive medication is both an old and an exciting idea. The Nature opinion piece also documents studies, beginning in the 1960s, which showed that psilocybin and LSD were effective treatments for Obsessive-Compulsive Disorder (OCD).  Other studies have shown alleged successes using low-dose ketamine for heroin addiction. And some of the earliest LSD studies of all showed impressive results when LSD and psychotherapy were combined as a treatment for alcoholism.

 By 1965, the authors claim, there were more than 1,000 published clinical studies on the therapeutic effects of psychedelics.  But many, if not most, of the early studies were marred by procedural problems, lack of control groups, and the fact that researchers from a dozen different disciplines, representing a dozen different experimental methods, predictably emphasized different kinds of experiential results.  The authors suggest that novel neuroimaging techniques combined with an increased understanding of molecular mechanisms of action mean that it will be different this time. If the only real result of the ketamine studies is increased funding for research on psychedelic drugs after a long hiatus, that is still progress, and it’s long overdue.

Resources

David Biello, Scientific American

Maia Szalavitz, New Scientist

and MSN Health and Fitness

Scicurious at Neurotic Physiology

Neuroskeptic at Neuroskeptic

Eugene Rubin, Psychology Today

Jonah Lehrer at Frontal Cortex

Photo Credit: http://cherished79.wordpress.com/