Know Your Powders

Update on Synthetic Drug Surprises

Spicier than ever.

Four drug deaths last month in Britain have been blamed on so-called “Superman” pills being sold as Ecstasy, but actually containing PMMA, a synthetic stimulant drug with some MDMA-like effects that has been implicated in a number of deaths and hospitalizations in Europe and the U.S. The “fake Ecstasy” was also under suspicion in the September deaths of six people in Florida and another three in Chicago. An additional six deaths in Ireland have also been linked to the drug. (See Drugs.ie for more details.)

PMMA, or paramethoxymethamphetamine, causes dangerous increases in body temperature and blood pressure, is toxic at lower doses than Ecstasy, and requires up to two hours in order to take effect.

In other words, very nearly the perfect overdose drug.

Whether you call them “emerging drugs of misuse,” or “new psychoactive substances,” these synthetic highs have not gone away, and aren’t likely to. As Italian researchers have noted, “The web plays a major role in shaping this unregulated market, with users being attracted by these substances due to both their intense psychoactive effects and likely lack of detection in routine drug screenings.” Even more troubling is the fact that many of the novel compounds turning up as recreational drugs have been abandoned by legitimate chemists because of toxicity or addiction issues.

The Spice products—synthetic cannabinoids—are still the most common of the novel synthetic drugs. Hundreds of variants are now on the market. Science magazine recently reported on a UK study in which researchers discovered more than a dozen previously unknown psychoactive substances by conducting urine samples on portable toilets in Greater London. Call the mixture Spice, K2, Incense, Yucatan Fire, Black Mamba, or any other catchy, edgy name, and chances are, some kids will take it, both for the reported kick, and for the undetectability. According to NIDA, one out of nine U.S. 12th graders had used a synthetic cannabinoid product during the prior year.

“Laws just push forward the list of compounds,” Dr. Duccio Papanti, a psychiatrist at the University of Trieste who studies the new drugs, said in an interview for this article. “The market is very chaotic, bulk purchasing of pure compounds are cheaply available from China, India, Hong-Kong, but small labs are rising in Western Countries, too. Some authors point out that newer compounds are more related to harms (intoxications and deaths) than the older ones. You can clearly see from formulas that newer compounds are different from the first ones: new constituents are added, and there are structural changes, so although we have some clues about the metabolism of older, better studied compounds, we don't know anything about the newer (and currently used) ones."

The problems with synthetic cannabinoids often begin with headaches, vomiting, and hallucinations. At the Department of Medical, Surgical, and Health Sciences at the University of Trieste, researchers Samuele Naviglio, Duccio Papanti, Valentina Moressa, and Alessandro Ventura characterized the typical ER patient on synthetic cannabinoids, in a BMJ article: “On arrival at the emergency department he was conscious but drowsy and slow in answering simple questions. He reported frontal headache (8/10 on a visual analogue scale) and photophobia, and he was unable to stand unassisted. He was afebrile, his heart rate was 170 beats/min, and his blood pressure was 132/80 mm Hg.”

According to the BMJ paper, the most commonly reported adverse symptoms include: "Confusion, agitation, irritability, drowsiness, tachycardia, hypertension, diaphoresis [sweating], mydriasis [excessive pupil dilation], and hallucinations. Other neurological and psychiatric effects include seizures, suicidal ideation, aggressive behavior, and psychosis. Ischemic stroke has also been reported. Gastrointestinal toxicity may cause xerostomia [dry mouth], nausea, and vomiting. Severe cardiotoxic effects have been described, including myocardial infarction…”

In a recent article (PDF) for World Psychiatry, Papanti and a group of other associates revealed additional features of synthetic cannabimemetics (SC), as they are officially known: “For example, inhibition of γ-aminobutyric acid receptors may cause anxiety, agitation, and seizures, whereas the activation of serotonin receptors and the inhibition of monoamine oxidases may be responsible for hallucinations and the occurrence of serotonin syndrome-like signs and symptoms.”

Papanti says researchers are also seeing more fluorinated drugs. “Fluorination is the incorporation of fluorine into a drug,” he says, one effect of which is “modulating the metabolism and increasing the lipophilicity, and enhancing absorption into biological membranes, including the blood-brain barrier, so that a drug is available at higher concentrations. An increasing number of fluorinated synthetic cannabinoids are available, and fluorinated cathinones are available, too.”

A primary problem is that physicians are still largely unacquainted with these chemicals, several years after their current popularity began. This is entirely understandable. In addition to the synthetic cathinones, several new mind-altering substances based on compounds discovered decades ago have also surfaced lately. Papanti provided a partial list of additional compounds that have led to official concern in the EU:

—Synthetic opioids (the best known are AH-7921, MT-45)

—Synthetic stimulants (the best known are MDPV, 4,4'-DMAR)

—New synthetic psychedelics (the NBOMe series)

—New dissociatives (Methoxetamine, Methoxphenidine, Diphenidine)

—New performance enhancing drugs (Melanotan, DNP)

—Gaba agonists (Phenibut, new benzodiazepines)

Most of the new and next-generation synthetics are not readily detected by standard drug screen processes. Spice drugs will not usually show up on anything but the most advanced test screening, using gas chromatography or liquid chromatography-tandem mass spectrometry—high tech tools which are rarely available for anything but serious (and costly) forensic investigations.

“Testing is a big problem,” Papanti declares. “From a clinical point of view, do you need the test to make a diagnosis of intoxication, for following up an addiction treatment, or for forensic purposes? With the new drugs, maybe taken together, with different pharmacology, we are not very sure about this yet. If I want to have confirmation of a diagnosis of SC intoxication, I need two weeks as an average, in order to obtain the result. Your patient has been discharged by that time, or in the worse case, he is dead.”

 Another major problem, according to Papanti, “is that the machines need sample libraries in order to recognize the compound, and samples mean money. Plus, they need to be continuously updated.”

In summary, there is no antidote to these drugs, but intoxication is general less than 24 hours, and the indicated medical management is primarily supportive. If you plan to take a drug marketed as Ecstasy, or indeed any of the spice or bath salt compounds, Drugs.ie notes that there are some basic rules of conduct that will help maximize the odds of a safe trip:

—If you don’t “come up” as quickly as anticipated, don’t assume you need another pill. PMMA can take two hours or more to take effect. Do not “double drop.”

—If you don’t feel like you expected to feel, and are noticing a “pins-and-needles” feeling or numbness in the limbs, consider the possibility that another drug is involved.

—Don’t mix reputed Ecstasy with other drugs, especially alcohol, as PMMA reacts very dangerously with excessive alcohol.

—Remember to hydrate, but don’t overhydrate. If you go dancing, figure on about a pint per hour.

Getting Spiced

Synthetic cannabis is stronger than it used to be.

First published 10/07/2013

I wish I could stop writing blog posts about Spice, as the family of synthetic cannabinoids has become known. I wish young people would stop taking these drugs, and stick to genuine marijuana, which is far safer. I wish that politicians and proponents of the Drug War would lean in a bit and help, by knocking off the testing for marijuana in most circumstances, so the difficulty of detecting Spice products isn’t a significant factor in their favor. I wish synthetic cannabinoids weren’t research chemicals, untested for safety in humans, so that I could avoid having to sound like an alarmist geek on the topic.  I wish I didn’t have to discuss the clinical toxicity of more powerful synthetic cannabinoids like JWH-122 and JWH-210. I wish talented chemists didn’t have to spend precious time and lab resources laboriously characterizing the various metabolic pathways of these drugs, in an effort to understand their clinical consequences. I wish Spice drugs didn’t make regular cannabis look so good by comparison, and serve as an argument in favor of more widespread legalization of organic marijuana.

A German study, published in Addiction, seems to demonstrate that “from 2008 to 2011 a shift to the extremely potent synthetic cannabinoids JWH-122 and JWH-210 occurred…. Symptoms were mostly similar to adverse effects after high-dose cannabis. However, agitation, seizures, hypertension, emesis, and hypokalemia  [low blood potassium] also occurred—symptoms which are usually not seen even after high doses of cannabis.”

The German patients in the study were located through the Poison Information Center, and toxicological analysis was performed in the Institute of Forensic Medicine at the University Medical Center Freiburg. Only two study subjects had appreciable levels of actual THC in their blood. Alcohol and other confounders were factored out. First-time consumers were at elevated risk for unintended overdose consequences, since tolerance to Spice drug side effects does develop, as it does with marijuana.

Clinically, the common symptom was tachycardia, with hearts rates as high as 170 beats per minute. Blurred vision, hallucinations and agitation were also reported, but this cluster of symptoms is also seen in high-dose THC cases that turn up in emergency rooms. The same with nausea, the most common gastrointestinal complaint logged by the researchers.

But in 29 patients in whom the presence of synthetic cannabinoids was verified, some of the symptoms seem unique to the Spice drugs. The synthetic cannabinoids caused, in at least one case, an epileptic seizure. Hypertension and low potassium were also seen more often with the synthetics. After the introduction of the more potent forms, JWH-122 and JWH-210, the symptom set expanded to include “generalized seizures, myocloni [muscle spasms] and muscle pain, elevation of creatine kinase and hypokalemia.” The researchers note that seizures induced by marijuana are almost unheard of. In fact, studies have shown that marijuana has anticonvulsive properties, one of the reason it is popular with cancer patients being treated with radiation therapy.

And there are literally hundreds of other synthetic cannabinoid chemicals waiting in the wings. What is going on? Two things. First, synthetic cannabinoids, unlike THC itself, are full agonists at CB1 receptors. THC is only a partial agonist. What this means is that, because of the greater affinity for cannabinoid receptors, synthetic cannabinoids are, in general, stronger than marijuana—strong enough, in fact, to be toxic, possibly even lethal. Secondly, CB1 receptors are everywhere in the brain and body. The human cannabinoid type-1 receptor is one of the most abundant receptors in the central nervous system and is found in particularly high density in brain areas involving cognition and memory.

The Addiction paper by Maren Hermanns-Clausen and colleagues at the Freiburg University Medical Center in Germany is titled “Acute toxicity due to the confirmed consumption of synthetic cannabinoids,” and is worth quoting at some length:

The central nervous excitation with the symptoms agitation, panic attack, aggressiveness and seizure in our case series is remarkable, and may be typical for these novel synthetic cannabinoids. It is somewhat unlikely that co-consumption of amphetamine-like drugs was responsible for the excitation, because such co-consumption occurred in only two of our cases. The appearance of myocloni and generalized tonic-clonic seizures is worrying. These effects are also unexpected because phytocannabinoids [marijuana] show anticonvulsive actions in humans and in animal models of epilepsy.

The reason for all this may be related to the fact that low potassium was observed “in about one-third of the patients of our case series.” Low potassium levels in the blood can cause muscle spasms, abnormal heart rhythms, and other unpleasant side effects.

One happier possibility that arises from the research is that the fierce affinity of synthetic cannabinoids for CB1 receptors could be used against them. “A selective CB1 receptor antagonist,” Hermanns-Clausen and colleagues write, “for example rimonabant, would immediately reverse the acute toxic effects of the synthetic cannabinoids.”

The total number of cases in the study was low, and we can’t assume that everyone who smokes a Spice joint will suffer from epileptic seizures. But we can say that synthetic cannabinoids in the recreational drug market are becoming stronger, are appearing in ever more baffling combinations, and have made the matter of not taking too much a central issue, unlike marijuana, where taking too much leads to nausea, overeating, and sleep.

(See my post “Spiceophrenia” for a discussion of the less-compelling evidence for synthetic cannabinoids and psychosis).

Hermanns-Clausen M., Kneisel S., Hutter M., Szabo B. & Auwärter V. (2013). Acute intoxication by synthetic cannabinoids - Four case reports, Drug Testing and Analysis,   n/a-n/a. DOI: 10.1002/dta.1483

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

LSD Mutates Into NBOMe

What’s on that blotter?

It is a darkly poetic indictment of the War on Drugs that LSD, the first synthetic psychedelic, demonized for decades and the target of extremely expensive law enforcement operations, looks to be far safer than its replacements.

—Earth and Fire Erowid, in Erowid Extracts

It is called 25I-NBOMe, or 2C-I-NBOMe, or SC-B-NBOMe, or, erroneously, 2C-I. It belongs to a group of drugs called the NBOMes, which are derived from phenethylamine-based drug families made infamous by Dr. Alexander Shulgin. The NBOMe part stands for N-Benzyl-Oxy-Methyl. After it was first synthesized in 2003, Purdue University did some research on the chemical structure of NBOMes, but it was not until 2010 that the drugs began to appear in the underground market.  25I-NBOMe, the most common variety, is strongly psychedelic, with vivid visual and sensory effects. It can also cause horrid trips, especially at higher doses, and like LSD, it can cause vasoconstriction in the form of elevated blood pressure.

Earth and Fire Erowid, editors of the well-regarded Erowid drug information site, wrote a special report on the NBOMes for the July Erowid Extracts.  It is worth going over in some detail.

The NBOMes were initially freebase powders, either snorted or held in the mouth, but the authors note that there is still confusion and uncertainty about the relative effectiveness of various forms of administration. In one case noted by Erowid, three friends obtained a bottle of 25-I-NBOMe, marked as 500 micrograms per drop. “Those who took one drop enjoyed the experience,” but one of the friends, “after three drops, became incoherent and frantic, then ran from the house and drove off in his car. He crashed into a tree and woke up in the hospital two days later….”

This suggests both high potency and a rapid ramp-up of negative effects with dosage, making the NBOMes generally unreliable as street drugs. As the article in Erowid Extracts notes, “The unusually high potency makes overdoses more likely. Unfortunately, the risks of 25I (and perhaps other NBOMes) at high doses seem to include delirious, dangerous behavior (with some accidents resulting in death), as well as the possibility of death from direct pharmacological effects. Medically dangerous doses may be as low as 3-5 mg.”

Even worse, 25I and 25C, when sold as powders, makes dosing even more precarious. Drugs this strong in powder form should only be handled by someone wearing Walter White-style hand and eye protection. “Many people have prior experience with insufflating small lines or bumps of a psychedelic or stimulant,” says Erowid. “It’s a fairly new phenomenon that a similarly-sized line of a drug could lead to death.”

On another note, the incredible potency of the NBOMes makes them imminently smuggleable. A single 750-mcg dose equals about 6 grains of table salt. You could hide about 100,000 doses of 25I in a soda pop can.

For historical perspective, the authors point to the DEA’s bust-up of global supply chains for LSD in the early 2000s. Figures from the Monitoring the Future survey show that use of LSD by 18 year-olds has gone from about 8% in 1999 to less than 2% by 2009. What to do with all that perforated blotter paper? One time-honored response from dealers is to dump a different chemical on the paper and sell it as LSD. Erowid reminds us that LSD sold as the more expensive and difficult-to-synthesize mescaline in the hippie heydays was an early example of this practice.  As one Erowid contributor put it, “Which do you think would sell better, blotter sold as ‘25I-NBOMe’ or blotter sold as the now nearly mythical ‘acid’?”

Erowid found that at the online drug  site Silk Road, NBOMes were being offered at prices 5 to 10 times cheaper than LSD. Silk Road sells 25B-NBOMe powder for between $90 and $200 a gram. Hit size is often 1 mg or more, which is definitely a large dose. Vendors at Silk Road also sell perforated blotter paper with classic acid blotter designs from the past, like Albert Hofmann and the Beatle’s Yellow Submarine.

All of this adds up to erroneous reports of death by LSD, amid actual overdoses caused by an incredibly powerful and relatively untested new drug with a murky track record. Acid is not a lethal drug, and no deaths by overdose have ever been clearly and directly attributed to LSD.

The state of Virginia banned the NBOMes last year, and so far this year, several other states and nations have joined in. But Erowid points out that the U.N.’s World Drug Report 2013 concluded that “no sooner is one substance scheduled, than another one replaces it, thus making it difficult to study the long-term impact of a substance on usage and its health effects.” All of which, says Erowid, begs the question of what drugs will pop up to replace 25I-NBOMe once it is banned? Erowid has high hopes for a landmark New Zealand bill calling for a vendor framework in which the drugs are sold legally only if registration, safety testing, and recordkeeping meet certain standards. The bill is expected to become law in New Zealand later this year.

As Erowid notes, other countries will be watching New Zealand closely. A report by the Health Officers Council of British Columbia points out that “Prohibiting a substance does send a message of social disapproval of use… but the value of using prohibition to send a message to dissuade use must be weighed against the harmful consequences of implementing prohibition….”

Photo Credit:  http://ewsd.wiv-isp.be 

MDPV Turns Lab Rats Into "Window Lickers"

Popular bath salt drug shown to be highly addictive.

Researchers at the Scripps Research Institute (TSRI) in La Jolla, California, appear to have hammered the last nail into the coffin for the common “bath salt” drug known as MDPV. We can now say with a high degree of certainty that, based on animal models, we know that 3,4-methylenedioxypyrovalerone is addictive—perhaps more strongly addictive than methamphetamine, although such comparisons are always perilous. However, principal investigator Michael A. Taffe, an associate professor at TSRI, said in a prepared release that the research group “observed that rats will press a lever more often to get a single infusion of MPDV than they will for meth, across a fairly wide dose range.”

Like methamphetamine, MDPV works by stalling the uptake of dopamine, and it also has effects on noradrenaline and serotonin.  As cathinone derivatives, MPDV and mephedrone are related to the stimulant drug khat, which is used like cocaine in northeastern Africa.  In earlier research at Scripps under Dr. Taffe, investigators found that lab rats would intravenously self-administer mephedrone and behave in a manner similar to the effects produced when the rats were on methamphetamine. In a paper  for Drug and Alcohol Dependence, the Taffe Lab concluded that “the potential for compulsive use of mephedrone in humans is likely quite high, particularly in comparison with MDMA.”

Now the researchers have zeroed in on the effects of the dirty pharmacology represented by MDPV, the other primary ingredient in many bath salt mixtures. In a new study by Michael Taffe, Tobin J. Dickerson, Shawn M. Aarde, and others, to be published in the August issue of Neuropharmacology, the investigators found that MDPV was a more potent attraction than meth for rats allowed to self-administer the drugs. Very little lab data exists for MDPV, and this study was among the first to directly compare the effect of MDPV to methamphetamine in an animal experiment.

It took some time to tease out the behavioral clues—the cognitive, thermoregulatory, and potentially addictive effects of the drug—but MDPV’s strong affinities with speed can no longer be ignored. The researchers saw the same types of repetitive activities seen in animals on meth, such as excessive grooming, tooth grinding, and skin picking.  Lead author Shawn Aarde said in a prepared statement that “one stereotyped behavior that we often observed was a rat repeatedly licking the clear plastic walls of its operant chamber—a behavior that was sometimes uninterruptable.”

 MDPV, in the jargon of such experiments, had “greater reward value” than methamphetamine. Which is saying something, given the well-publicized addictive threat of speed. When the group boosted the number of lever presses needed for another infusion of MDPV or meth, “we observed that rats emitted about 60 presses on average for a dose of meth but up to about 600 for MDPV—some rats would even emit 3,000 lever presses for a single hit of MDPV,” said Aarde in a press release. “If you consider these lever presses a measure of how much a rat will work to get a drug infusion, then these rats worked more than 10 times harder to get MDPV.”

Excuse me, did he say as many as three thousand bar presses for another bump of intravenous MDPV? He did. Overall, the rats self-administered more MDPV than methamphetamine. In the paper itself, the authors write that “compared with meth, the effect of MDPV on drug-reinforced behavior was of greater potency (more responding under lowest dose under fixed-ratio schedule) and greater efficacy (more responding under optimal dose under a progressive ratio schedule)…”

The conclusion? MDPV’s “abuse liability” may be greater than that of standard methamphetamine. Which is another excellent piece of evidence for approaching the world of new synthetic psychoactives with great caution.

Aarde S.M., Huang P.K., Creehan K.M., Dickerson T.J. & Taffe M.A. (2013). The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: Self-administration and locomotor activity in rats, Neuropharmacology, 71  130-140. DOI: 10.1016/j.neuropharm.2013.04.003

Popular Synthetics: The Class of 2013

Navigating the new alphabet of intoxication.

You don’t have to be a molecular chemist to know which of today’s recreational drugs are safe. Wait, I take that back. You DO have to be a molecular chemist to navigate today’s synthetic drug market with anything like a modest degree of safety.

It’s hard not to get nostalgic: Back in the day, you had your pot, you had your acid, your coke, your speed, and your heroin. And that, with the exception of a few freak outriders like PCP, was about that. Baby boomers of today, already losing touch with leading-edge music—Macklemore? Tame Impala?—can now consider themselves officially out of touch when it comes to illegal drugs.

That is, unless they are familiar with psychoactive chemicals beyond mere methamphetamine “bath salt” knockoffs like mephedrone, and cannabis “Spice” look-alikes such as JWH-018. We’re talking about drugs like Bromo-DragonFly, Benzo Fury, and 2C-B.  As Vanessa Grigoriadis writes in New York Magazine: “These drug users imagine themselves as amateur chemists, proto-Walter Whites, sampling and resynthesizing drugs to achieve exactly the state of consciousness they find most pleasurable. And there are no end of drugs to play with.”

A big piece of the synthetic drugs movement can be traced to the work of the legendary Alexander Shulgin, a Harvard grad who worked for Dow chemical, and who invented more than 100 entirely novel hallucinogenic compounds over the years. Other than the hallucinogens investigated by Shulgin and his coterie of personal friends, who were willing to take new hallucinogens and report back, none of the drugs on this list were meant for, or tested on, human beings.

Many of them are not, technically, new. Nonetheless, writes Grigoriadis, "almost every drug, from pot to GHB to morphine, has been messed with, as chemists find that removing a methoxy group or adding a benzene ring makes a new drug with different properties: body-grooving with a side helping of visuals, euphoric or speedy, long or short, or administering just the right dose of primal fear. Formerly known as “designer drugs,” they have morphed into “synthetic highs.” The tricky precursor chemical problem has become much easier to solve in the present moment, when any budding entrepreneur can send the official chemical designation of a drug, called its CAS number, to any of dozens of manufacturers in China, who will provide them with whatever weird “research” drug they need.


Herewith, a sampling of a few popular drugs of the day:

• 2C Series

2C-P is an Alexander Shulgin favorite, a hallucinogenic phenethylamine known officially as 2-(2,5-dmethoxy-4-propylphenyl)ethanamine. But your mileage may vary. Phenethylamine is similar in action to amphetamine and acts on dopamine and norepinephrine receptors. Nonetheless, 2C drugs have strong psychedelic effects as well. Other phenethylamine drugs include ephedrine, mescaline, bupropion (Wellbutrin), and venlafaxine (Effexor). There are several drugs in the 2C family, including 2C-B and 2C-I, but 2C-P is considered the strongest in the class, an intense psychedelic with visualizations lasting for up to 16 hours. 2C-B, or 4-bromo-2,5-dimethoxyphenethylamine is another popular hallucinogen, described by some as a cross between LSD and MDMA (Ecstasy)—less “psychedelic” than LSD, with stronger “body effects.” Drugs in this family are generally recognized as non-addictive, but large doses can cause sweating and chills, stomach discomfort, and paranoia or panic. A close cousin, the DOB drugs (2,5-Dimethoxy-4-Bromoamphetamine) are a related family of hallucinogens.

• Bromo-Dragonfly

This synthetic, sold as 3C-Bromo-Dragonfly and DOB-Dragonfly, is a very strong serotonin agonist, and has effects consistent with serotonin 5-HT hallucinogens such as LSD. This one came out of Purdue Pharmaceuticals as a compound for use in serotonin research, and belongs to a class of drugs called benzodifurans, which are related to the phenethylamines. It has been implicated in several deaths since it was first reported in 2007, says drug site Erowid. Positive effects listed at EROWID  included mood lift, visual changes, and increased energy. Negative effects include short-term memory loss, muscle tension, and “unknown risks due to research chemical status.” This is not a drug to take lightly. Dr. Jeff Lapoint, an attending physician at San Diego’s Kaiser Permanente and an expert in toxicology, recently told Tony O'Neill at The Fix that “Bromo-Dragonfly is probably the scariest thing on the list.”

• NBOMe Series

This group of synthetics, now available to underground buyers, is a perfect example of a complicated new series of psychoactive drugs with little or no track record of human use before they appeared online in 2010. When coherently labeled at all, they are sold as 2C-C-NBOMe, 2c-I-NBOMe, 25C-NBOMe, and mescaline-NBOMe, among other designations. The NBOMe series have attributes of both hallucinogens and amphetamines, and are active at very low doses, like LSD. There isn’t even much in the way of animal research on this collection. As with many of these synthetics, reports linking 2C-C-NBOMe to the deaths of young users have surfaced over the past two years.  While hallucinogens always present this Janus-faced aspect, this roll-the-dice-for-a-good-trip-or-a-bad-trip vibe, the ability to actually KNOW what you are taking—always a problem of major significance in the underground drug world—becomes even more acute in the case of research chemicals not intended for human use, let alone Prime Time.  If all goes well, users get a mood lift, visuals, and euphoria. At high doses, the effects can include nausea, paranoia, extreme fear, and panic. It is the essential dilemma at the heart of psychedelic experimentation—there are no guarantees going in, and it is always, at least to a degree, a form of psychic Russian roulette.

• 6-APB (Benzo Fury)

A lot of different drugs are sold as Benzo Fury, but the name comes originally from 6-APB, or 6-(2-aminopropyl)benzofuran. Like so many other designer amphetamines, 6-APB showed up online in 2010. The online drug discussion site Bluelight notes that vendors also peddle it as 6-APDB, 5-APDB, and 4-D as well. To date it has mostly surfaced as a club drug in the UK, and is chemically similar to MDA, another “entactogen” with strong body effects that was popular in the 60s as the “love drug.” Unfortunately Benzo Fury proved to be such a Euro-smash as a brand that drug sellers started packaging any research chemical at hand as Benzo Fury, so that the brand name has already become meaningless.

• MDPV

3,4-methylenedioxypyrovalerone, frequently referred to as bath salts, or sometimes as Molly, which is supposed to mean MDMA, is primarily a methamphetamine-style stimulant, but can induce hallucinations at high doses, EROWID reports, as well as tachycardia and elevated blood pressure. As with speed, withdrawal can be extremely problematic, and increased mental and physical energy make this one highly reinforcing. Redosing is common. Recent studies strongly suggest that it is addictive in humans. A report at EROWID states: “Doing/coming off of MDPV is like winning a Mercedes and being told at the last minute they got your name wrong. Uggh.”

• 5-MeO-DMT

This naturally occurring hallucinogenic tryptamine, 5-methoxy-N,N-dimethyltryptamine by name, has the unfortunate luck of sounding like another drug, simply called DMT. Both have hallucinogenic properties, but vaporized 5-MeO-DMT is active at 5 mg, where DMT is only active at a dosage about 5 times that high. So confusing the two drugs is not wise. High doses of 5-MeO-DMT can cause cardiac problems, convulsions, and mental confusion. Dealers who use them interchangeably are to be avoided. Unlike some of the other drugs in this list, 5-MeO-DMT has a long pedigree, in use since the 1970s, and is thought by some anthropologists to have been an ingredient in “shamanic snuff” used by early civilizations.

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

Popular “Bath Salt” Hooks Lab Rats

Mephedrone shows addictive properties in animal models.

Cathinones, like methedrine and other stimulants, are primarily dopamine-active drugs. Though they are now illegal in the U.S., they were formerly of primary interest only to pharmaceutical researchers. The best-known cathinone sold in the form of bath salts and plant food—mephedrone—has both dopamine and serotonin effects. It broke big in the UK a few years ago as a “legal” party drug alternative to MDMA. The idea was to get high without testing dirty, as the saying goes.

Behavioral clues about mephedrone have been teased out of rat studies. The Taffe Laboratory at Scripps Research Institute has been focusing on the cognitive, thermoregulatory, and potentially addictive effects of the cathinones, and mephedrone in particular. Scripps researchers have carried the investigation forward with a recent study in the journal Drug and Alcohol Dependence.

Now comes additional evidence, also from the Taffe Lab at Scripps, that mephedrone, or 4-MMC, looks like an addictive drug. In a paper accepted for publication by Addiction Biology, which Addiction Inbox was allowed to review in advance, Dr. Michael Taffe, along with lead author S.M. Aarde and coworkers, demonstrated in an animal study that lab rats will intravenously self-administer mephedrone under normal lab conditions—roughly analogous to shooting speed.

Without suitable strains of test animals, most genetic and neurobiological research would take centuries, and would involve ethical questions about human testing far stickier than the questions raised by work with animals. Animal models are one of the primary pathways of discovery available to neurobiologists and other researchers.

But it’s tricky. Establishing traditional rodent laboratory conditions is a Goldilocks endeavor: The environment must be not too hot, but not too cold, because this can effect rodent behavior. And the drug must be given at rates that are not too frequent and not too rare.

The curious thing about mephedrone is that it appears to combine the effects of prototypical stimulants like cocaine and methamphetamine, with the trippy, “entactogen” effects of MDMA, aka Ecstasy, in the bargain. The drug rapidly crosses the blood-brain barrier, reaching peak levels two minutes after injection, and full effects last about an hour. In one study, 76% of people who had snorted both cocaine and mephedrone reported that the quality of the mephedrone high was “similar to or better than” cocaine. But the paper also states that “human recreational users report 4-MMC to be subjectively similar to MDMA.”

The investigators ran a series of tests with various groups of rats, and found that 80-100% of the rats would happily reward-press a lever for an infusion of mephedrone. “Under these conditions,” writes Taffe, “methamphetamine and 4-MMC have about equal effect on rat self-administration although the 4-MMC is considerably less potent, requiring about 10 times the per-infusion dose for effect.” Although it wasn’t demonstrated directly in this paper, Ecstasy “is at best unevenly self-administered by rats,” and “despite an MDMA-like serotonin/dopamine neuropharmacological effect, mephedrone has a liability for repetitive intake more similar to the classical amphetamine-type stimulants such as methamphetamine.”

It’s a weaker type of stimulant, mephedrone, but it does the trick. It is highly reinforcing. Mephedrone chemically resembles speed, but also has Ecstasy-like effects. "Furthermore, neurochemical data suggest MDMA-like patterns of relatively greater serotonin versus dopamine accumulation in nucleus accumbens.” Even with its added Ecstasy-like effects, the scientists conclude that “the potential for compulsive use of mephedrone in humans is likely quite high, particularly in comparison with MDMA.”

Photo Credit: Creative Commons

Synthetic Drugs: Collected Posts

Catching up with bath salts and spice.


The Low Down on the New Highs: Not all bath salts are alike.

“You’re 16 hours into your 24-hour shift on the medic unit, and you find yourself responding to an “unknown problem” call.... Walking up to the patient, you note a slender male sitting wide-eyed on the sidewalk. His skin is noticeably flushed and diaphoretic, and he appears extremely tense. You notice slight tremors in his upper body, a clenched jaw and a vacant look in his eyes.... As you begin to apply the blood pressure cuff, the patient begins violently resisting and thrashing about on the sidewalk—still handcuffed. Nothing seems to calm him, and he simultaneously bangs his head on the sidewalk and tries to kick you...” [Go here]


The New Highs: Are Bath Salts Addictive? What we know and don’t know about synthetic speed.

Call bath salts a new trend, if you insist. Do they cause psychosis? Are they “super-LSD?” The truth is, they are a continuation of a 70-year old trend: speed. Lately, we’ve been fretting about the Adderall Generation, but every population cohort has had its own confrontation with the pleasures and perils of speed: Ritalin, ice, Methedrine, crystal meth, IV meth, amphetamine, Dexedrine, Benzedrine… and so it goes. For addicts: Speed kills. Those two words were found all over posters in the Haight Ashbury district of San Francisco, a few years too late to do the residents much good…. [Go here]


“Bath Salts” and Ecstasy Implicated in Kidney Injuries: “A potentially life-threatening situation.”

Earlier this month, state officials became alarmed by a cluster of puzzling health problems that had suddenly popped up in Casper, Wyoming, population 55,000. Three young people had been hospitalized with kidney injuries, and dozens of others were allegedly suffering from vomiting and back pain after smoking or snorting an herbal product sold as “blueberry spice.” The Poison Review reported that the outbreak was presently under investigation by state medical officials.  “At this point we are viewing use of this drug as a potentially life-threatening situation,” said Tracy Murphy, Wyoming state epidemiologist…. [Go here]


The Triumph of Synthetics: Designer stimulants surpass heroin and cocaine.

A troubling report by the United Nations Office on Drugs and Crime (UNODC) shows that amphetamine-type stimulants (ATS) have, for the first time, become more popular around the world than heroin and cocaine. Marijuana remains the most popular illegal drug in the world, and the use of amphetamines has fallen sharply in the U.S., but the world trend represents the worldwide triumph of synthetic drug design over the plant-based “hard drugs” of the past…. [Go here]

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…. [Go here]


An Interview with Pharmacologist David Kroll: On synthetic marijuana, organic medicines, and drugs of the future.

Herewith, a 5-question interview with pharmacologist David Kroll, Ph.D., Professor and Chair of Pharmaceutical Science at North Carolina Central University in Durham, and a well-known blogger in the online science community. A cancer pharmacologist whose field is natural products—he’s currently involved in a project to explore the potential anticancer action of chemicals found in milk thistle and various sorts of fungi—Dr. Kroll received his Ph.D. from the University of Florida, and completed his postdoctoral fellowship in Medical Oncology and Molecular Endocrinology at the University of Colorado School of Medicine. He went on to spend the first nine years of his independent research and teaching career at the University of Colorado School of Pharmacy, where he taught all aspects of pharmacology, from central nervous system-active drugs, to anticancer and antiviral medications…. [Go here]


Mephedrone, the New Drug in Town: Bull market for quasi-legal designer highs.

Most people in the United States have never heard of it. Very few have ever tried it. But if Europe is any kind of leading indicator for synthetic drugs (and it is), then America will shortly have a chance to get acquainted with mephedrone, a.k.a. Drone, MCAT, 4-methylmethcathinone (4-MMC), and Meow Meow--the latter nickname presumably in honor of its membership in the cathinone family, making it chemically similar in some ways to amphetamine and ephedrine. But its users often refer to effects more commonly associated with Ecstasy (MDMA), both the good (euphoria, empathy, talkativeness) and the bad (blood pressure spikes, delusions, drastic changes in body temperature)…. [Go here]


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…. [Go here]


The New Cannabinoids: Army fears influx of synthetic marijuana.

It’s a common rumor: Spice, as the new synthetic cannabis-like products are usually called, will get you high--but will allow you to pass a drug urinalysis. And for this reason, rumor has it, Spice is becoming very popular in exactly the places it might be least welcomed: Police stations, fire departments—and army bases. What the hell is this stuff? [Go here]

Photo credit: http://gizmodo.com/

photo credit 2: http://www.clemson.edu/

The Triumph of Synthetics

Designer stimulants surpass heroin and cocaine.

A troubling report by the United Nations Office on Drugs and Crime (UNODC) shows that amphetamine-type stimulants (ATS) have, for the first time, become more popular around the world than heroin and cocaine. Marijuana remains the most popular illegal drug in the world, and the use of amphetamines has fallen sharply in the U.S., but the world trend represents the worldwide triumph of synthetic drug design over the plant-based “hard drugs” of the past.

The 2011 Global ATS Assessment estimates that in 2009, some 14 to 57 million people aged 15-64 took an amphetamine-type substance during the year.  The category includes methamphetamine, synthetic stimulants known as bath salts, and Ecstasy. For ecstasy, which is grouped with the ATS family because of its speed-like qualities, “global annual prevalence” stood at only 11-28 million past-year users in 2009, basically unchanged.  Not so for the use of the new synthetic methamphetamines—compounds such as mephedrone, 4-methylmethcathinone (4-MMC) and MDPV, which first took off in the UK, Canada, and New Zealand. In fact, bath salts in the form of mephedrone are competing with ecstasy as the club drug of the moment. (Ecstasy seizures are currently at a 5-year high in the United States, so the window for alternatives is currently wide open.) Meanwhile, recorded worldwide use of heroin, cocaine, and marijuana remained essentially steady from 2005 to 2009.

So what’s behind the global surge in production of amphetamine-type drugs? What advantages do these stimulants hold over time-tested drugs like heroin and coke?  And why is it happening now?

                                                      Emerging Markets

The seismic changes in worldwide drug production begin with geography. Amphetamine-type stimulants are spreading to new regions, and are now being manufactured in places previously off the radar—Iran, Malaysia, and West Africa, for starters. The UNODC report notes that synthetic stimulants “offer criminals a new entry into unexploited and fresh markets.” The locus of activity is no longer the opium fields of Afghanistan, or the coca plantations of Columbia. In absolute numbers, the report claims, “most ATS users live in Southeast Asia, the most populous subregion the world.”

The growing number of methamphetamine pills seized in Southeast Asia is staggering: “The 93.3 million methamphetamine pills seized in 2009 in China, Lao People’s Democratic Republic, Myanmar and Thailand represent a three-fold increase in comparison with 2008 figures,” the UN report alleges. “In 2010, total seizures surpassed 133 million pills.” Not since the Japanese amphetamine scourge of the post-World War II years has East Asia seen anything like this.

 The UN report singles out two new countries—Lao People’s Democratic Republic, and Malaysia—as nations reporting, for the first time, “the injecting use of crystalline methamphetamine in 2008 and 2009.” And a massive increase in production has been documented in northern Burma. Voice of America News reports that amphetamine-type drug seizures in Burma went from one million pills in 2008 to a mind-blowing 23 million pills a year later.

A regional representative for the UNODC in East Asia said that the seizures “reflect a dramatic increase in production in the Shan State” in Northern Burma. The production of methamphetamine is a primary source of income for the Shan, whose territory is near the borders of China and Thailand. “What we are worried about,” said the UNODC rep, “is the nexus of drugs, of weapons, of money that is moving around that region at a time when elections are pending and the political situation is quite fragile.” At the same time, Burma remains a major supplier of opiates, though competition with Afghanistan may have helped encourage the production of illegal stimulants. UNODC Executive Director Yury Fedotove explained that the market for synthetic stimulants “has evolved from a cottage-type industry typified by small-scale manufacturing operations to more of a cocaine or heroin-type market with a higher level of integration and organized crime groups involved throughout the production and supply chain.“

                                                    Homegrown vs. Manmade

Amphetamines, in all their synthetic forms, have several production advantages over plant-based addictive drugs like heroin and cocaine. In recent years, the U.S. and other countries have cracked down on amphetamine precursor drugs like ephedrine and pseudoephedrine. Once these tried and true compounds for amphetamine manufacture—found in cold and allergy medications—were registered and controlled, traffickers made the switch to different chemical approaches. New building blocks like phelylacetic acid and l-phenylacetylcarbinol (l-PAC) have been found in labs from Canada to Mexico. Growers of opium and coca have no such alternatives available to them. Pharmacologist David Kroll, Professor and Chair of Pharmaceutical Science at North Carolina Central University in Durham, who has been following the new synthetic drug products on his blog, Terra Sigillata, said that ome of the latest precursors have a problematic history. “Phenylacetate and phelylacetic acid have been investigated in clinical trials for cancer and in the treatment of sickle cell disease,” said Dr. Kroll. “But they didn’t fare well in large clinical trails because they required such high doses, and patients had side effects.”

While this is definitely not a reliable class of compounds from which to fashion new recreational stimulants, Dr. Kroll noted that rendering synthetic drugs illegal can sometimes play havoc with efforts to develop the same drugs for therapeutic purposes. “If these precursors become more strictly regulated, there might be an untoward effect on the prices of other drugs” that use the same compound as a building block, he said.

                                                               New Players

Drug lab seizures in Jordan, Syria, and the United Arab Emirates have also reached new highs—particularly the clandestine manufacture of a form of amphetamine called phenethylline, marketed under the brand name Captagon. Very little in the way of equipment or startup capital is required, which facilitates new players in this market. Captagon, said Dr. Kroll, “makes pretty good sense. The body can metabolize it to amphetamine itself—it’s an amphetamine pro-drug. The other metabolite of the drug is theophylline, the old asthma drug that also acts as a mild stimulant. But it’s potentially as dangerous as amphetamine, depending on how efficient one’s metabolism is.” This is, of course, a huge problem: One bath salts user might have an acceptable drug experience, while another might find that a few whiffs of the same synthetic stimulant will land him or her in the emergency room, with a dangerously elevated heart rate or other complications.

What drug designers, drug manufacturers, and drug suppliers have come to realize is that methamphetamine and other ATS drugs appear to fill the lifestyle void left by the uncertain supply and pricing situation associated with cocaine. Everywhere they land, synthetic stimulants—from biker crank to mephedrone—wreak instant havoc. They simply are not predictable compounds. One bath salts user compared the experience to “a shot of methamphetamine with a PCP chaser." From any kind of rational sociocultural point of view, these are not safe drugs. And it hardly needs repeating that they are highly addictive for many people. The legalization of amphetamine is not a cause likely to gain much momentum any time soon.

Even though the United States has a long history of dealing with amphetamine, this is manifestly not true of every country in the world. And now these untapped markets are fair game for cheaper, longer lasting amphetamine-type stimulants, which “seem to appeal to the needs of today’s societies and have become part of what is perceived to be a modern and dynamic lifestyle,” according to the UNODC report.

We don’t know with complete certainty that the drug data coming out of several key areas—Southeast Asia, Africa, and the Middle East in particular—is accurate. Authorities have captured and dismantled ATS labs in Central and South America as well. In all likelihood, drug production and use in all these regions is underreported. The UNODC document laments that “household and other surveys are lacking or are outdated in some countries in several of the most affected regions.” This is a particular problem in China and India, where no serious national survey of amphetamine-type stimulants has ever been undertaken.

We have a long way to go before we know the outcome of the current craze for synthetic stimulants. The historical wreckage caused by injected methedrine in the 60s and 70s, and smokable ice in the 90s and the aughts, is a grisly matter of public record. Now we are confronted with a baffling cornucopia of designer concoctions whose track record for safe recreation is, thus far, not so good. Amphetamine drugs have sent thousands to their deaths, and countless others to the emergency rooms. And now this deadly deck of stimulants has many more cards in it than it did just a few years ago. Pick a card, any card. First one’s free.

Photo Credit: http://teens.drugabuse.gov/

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

Bath Salts, Graphically

What you need to know about mephedrone.

The Pat Moore Foundation has put together this nifty chart as a primer on mephedrone, the amphetamine-type stimulant marketed as "bath salts." Thanks PMF! 

 Created by Pat Moore Foundation

Drug Czar “Deeply Concerned” About Synthetic Stimulants

“Bath salts” come under federal scrutiny.

The Director of the Office of National Drug Control Policy issued a warning about the new synthetic stimulants now being clandestinely marketed as bath salts or insecticide.  Admitting that “we lack sufficient data to understand exactly how prevalent the use of these stimulants are,” Drug Czar Gil Kerlikowske nonetheless announced that the marketing of such drugs as mephedrone and MDPV was “both unacceptable and dangerous.”

A growing list of states, now including Michigan, Hawaii, Louisiana, Kentucky, North Dakota, and, recently, Florida, have introduced measures to ban the designer drugs, currently being sold under names like “Ivory Wave” or “Purple Wave.” The United Kingdom has already put mephedrone and related drugs under a blanket ban. The drugs are considered addictive, primarily because they are chemically similar to amphetamine and ephedrine. But users often refer to effects more commonly associated with Ecstasy (MDMA), both the good (euphoria, empathy, talkativeness) and the bad (blood pressure spikes, delusions, drastic changes in body temperature).

“I am deeply concerned  about the distribution, sale, and use of synthetic stimulants—especially those that are marketed as legal substances,” Kerlikowske said. “I ask that parents and other adult influences act immediately to discuss with young people the severe harm that can be caused” by such drugs.

Kerlikowske, who will convene a panel of experts on the subject,  said he was acting in response to recent data from the American Association of Poison Control Centers, which showed that poison control units have received 251 calls related to “bath salts” so far this year, compared to a total of 236 calls in all of calendar year 2010.

An earlier post of mine on mephedrone can be found HERE. Some of the best coverage has come from the anonymous NIH researcher who blogs on science topics as DrugMonkey.  See also coverage of alleged mephedrone deaths by David Kroll HERE.


Photo Credit: http://www.astantin.com/

Khat to the Chase

Of mephedrone, bath salts, and impaired driving.

 Automobile accidents are the ninth leading cause of death worlwide, according to the World Health Organization (WHO). More than a million people are killed on roads annually, and that number could rise to 2.5 million by 2020. WHO estimates that traffic accidents cost developing countries an astonishing 1-2 % of their gross domestic product (GDP).

For years now, police and public health officials have puzzled over the alarming number of traffic accidents in East Africa. In terms of sheer numbers, Asian countries have the highest total traffic fatalities, according to figures compiled by the Global Road Safety Partnership (GRSP), a consortium including the World Bank, the Red Cross and other aid agencies (PDF HERE). That is not surprising, since these nations contain the majority of the world’s drivers.

However, beyond the picture of traffic fatalities in terms of sheer numbers, or on a per population basis, there is another revealing measure—traffic deaths per motor vehicle. And when the GRSP measured nations by that yardstick, the four worst countries in the world for traffic deaths—judging by the number of fatalities per 10,000 licensed vehicles—were Ethiopia, Tanzania, Lesotho, and Kenya—all East African nations.

Moreover, these are all African countries in which the use of khat--an amphetamine-like plant drug that is the natural precursor of the designer drug known as mephedrone--is legal and common. The major khat-using countries in Africa are commonly listed as: Somalia, Kenya, Yemen, Ethiopa, Tanzania, Lesotho. Note the overlap. Khat, as one online article put it, is “the legal high of east Africa.”

On the tiny island nation of Mauritius, just off the southeast African coast, Touria Prayag writes at allAfrica.com that drivers “zoom past you, zigzag on the roads, nervously changing to the left lane to swiftly veer back on your side without any warning…. brazenly flouting the Highway Code in every imaginable dangerous manner…. And the carnage continues….”

In Ethiopia, annual road crash fatalities account for 114 deaths per 10,000 vehicles, compared to one death per 10,000 vehicles in Great Britain, and an average of 60 deaths per 10,000 vehicles across 39 sub-Saharan African countries. A report in the Bulletin of the World Health Organization (PDF HERE)  notes that Ethiopian truck drivers “are regarded as so dangerous that their trucks are commonly referred to across Ethiopia as ‘al Qaeda.’” Anecdotally, Ethiopians told WHO officials that khat “increased driver confidence and vehicle speed while also making drivers irritable and impairing concentration,” and that high levels of khat could lead to hallucinations.

A Kenya forum on TripAdvisor asks: Are matatus [local taxes piloted by khat-chewing Kenyans] safe?” 

Since khat is legally available in most of East Africa, and comprises a significant part of the social fabric of local cultures, the use of khat is similar to the use of alcohol in higher-income nations. But does khat present the same threat of driving impairment as alcohol? Bolivia is now arguing its right to allow citizens to chew coca leaves in the traditional manner. Is it safe to drive and chew coca leaves? In all of these cases, the challenge is to determine what constitutes a “safe” dose of the drug; a dose that does not endanger people on or near the highway. There is not enough research on khat to answer that question. Nor is there a way to administer roadside tests for khat. The best evidence, African police officers say, is green teeth.

The active ingredients in khat—cathine and cathinone—are similar in structure to amphetamines, and chemically similar to the ingredients used in the manufacture of mephedrone powder. Mephedrone is sold as 4-MMC, Meow Meow, M-Cat, and other nicknames. Cathine and cathinone ramp up dopamine, serotonin and noradrenaline levels in a manner very similar to amphetamine, with many of the same positive effects (mild euphoria, reduced hunger, increased energy) and the same negative effects (depression, fatigue, lack of appetite, drug craving). It is thought that chronic use of khat results in dopamine D2 depletion in areas of the brain involved in goal-directed action.

The current fervor over mephedrone being disguised as bath salts or plant food for black market sales purposes in the U.S and U.K. demonstrates that this question is not academic for developed western nations. Sold as Ivory Wave, or Bliss, or White Lightning, mephedrone and other products containing cathinone are increasingly available across the U.S. states. In 2008, police seized 600 pounds of fresh khat—in Fargo, North Dakota.

A recent paper published in Frontiers in Psychology, authored by a group of Dutch and Spanish psychologists, appears to show that khat users exhibit a specific cognitive deficit: On stop-signal tasks, stop signal reaction time (SSRT) was significantly slower for the khat users. Such tests typically involve rapidly pressing a green “go” button upon seeing an arrow in certain positions, or abruptly aborting the response when the arrow turns red. The test measures “individual ability to stop a planned or ongoing motor response in a voluntary fashion.” For example, someone with Parkinson’s disease would score at the very high end of the SSRT scale.

The study itself involved 20 regular khat users recruited from the immigrant populations of Leiden and The Hague, and matched against 20 khat-free controls. All of the khat users met four or more of the 7 DSM-IV criteria for addiction, and did not consume alcohol the night before the test. The investigators speculate that this reduced level of inhibitory control “may even be involved in the emergence of addiction: the more a drug is used, the less able users are to prevent themselves from using it.”

The parallels to traffic signals and stop signs are obvious, and apt. The authors state that the findings of their study are “rather worrying because, first, many real-life situations require active inhibition of prepotent actions, as in the case of traffic lights turning red, or of criminal actions.” The obvious conclusion is that the chronic chewing of khat leaves “may indeed lead to a marked deterioration of cognitive functions (as inhibitory control) implicated in driving behavior.” Studies by NIDA director Nora Volkow and others have show that cocaine users suffer similar reductions in dopamine D2 receptors and “need significantly more time to inhibit responses to stop signals than non-users.” In general, stimulant drugs taken regularly at high doses appear to disrupt response inhibition due to alterations in dopamine functioning. (Although some studies have shown a facilitation of inhibitory control at lower doses).

The usual caveats apply: It is impossible to rule out pre-existing propensities for impulsivity, disinhibition, and the like. Some health researchers do not agree that the case for driving impairment on khat has yet been made. In the Bulletin of the World Health Organization, Anita Feigin of the Centre for Population Health in Australia writes that, so far, much of the information is anecdotal, “and, as yet, there is no clear evidence of a causal relationship between the use of khat and traffic accidents.” African taxi drivers who immigrate to Australia use khat “to stay awake and alert.” However, Feigin notes that the use of khat has deeply divided the members of east African migrant communities.

It is an interesting conundrum. The developed West has its entrenched tradition of alcohol as a legal high, despite its side-effects, which frequently result in mayhem on the highways. On the other hand, the drinking nations must now contend with demands from other cultures for the decriminalization of khat and coca leaf, which, along with coffee and tea, make up a category we might call the “soft” stimulants.

Because of the connection with mephedrone and other amphetamine-like designer drugs, these questions will not be going away until more research provides some solid answers. Such research may not be long in coming: The NIH-funded Khat Research Program (KRP) at the University of Minnesota, for example, brings American researchers together with a broad group of scientists from Yemenese and German universities to study the effects of a common plant drug most Americans have never heard of—but a drug they may be dealing with in synthetic form sooner rather than later.

Colzato, L., Ruiz, M., van den Wildenberg, W., Bajo, M., & Hommel, B. (2011). Long-Term Effects of Chronic Khat Use: Impaired Inhibitory Control Frontiers in Psychology, 1 DOI: 10.3389/fpsyg.2010.00219


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DEA Slaps Temporary Ban on Spice and Other “Fake Pot” Products

Synthetic cannabis now illegal for one year.

The material below is excerpted directly from the official press release of the U.S Drug Enforcement Administration Public Affairs Office:

The United States Drug Enforcement Administration (DEA) is using its emergency scheduling authority to temporarily control five chemicals (JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol) used to make “fake pot” products.  Except as authorized by law, this action will make possessing and selling these chemicals or the products that contain them illegal in the U.S. for at least one year while the DEA and the United States Department of Health and Human Services (DHHS) further study whether these chemicals and products should be permanently controlled. 

A Notice of Intent to Temporarily Control was published in the Federal Register today to alert the public to this action. After no fewer than 30 days, DEA will publish in the Federal Register a Final Rule to Temporarily Control these chemicals for at least 12 months with the possibility of a six-month extension. They will be designated as Schedule I substances, the most restrictive category, which is reserved for unsafe, highly abused substances with no medical usage.

Over the past year, smokable herbal blends marketed as being “legal” and providing a marijuana-like high, have become increasingly popular, particularly among teens and young adults.  These products consist of plant material that has been coated with research chemicals that mimic THC, the active ingredient in marijuana, and are sold at a variety of retail outlets, in head shops and over the Internet.  These chemicals, however, have not been approved by the FDA for human consumption and there is no oversight of the manufacturing process.  Brands such as “Spice,” “K2,” “Blaze,” and “Red X Dawn” are labeled as incense to mask their intended purpose.

Graphics Credit: http://thefreshscent.com/