Friday, February 27, 2015

The Blunt Facts About Blunts

Mixing tobacco with marijuana.

People who smoke a combination of tobacco and marijuana, a common practice overseas for years, and increasingly popular here in the form of “blunts,” may be reacting to some unidentified mechanism that links the two drugs. Researchers believe such smokers would be well advised to consider giving up both drugs at once, rather than one at a time, according to an upcoming study in the journal Addiction.

Clinical trials of adults with cannabis use disorders suggest that “approximately 50% are current tobacco smokers,” according to the report, which was published in the journal Addiction, and authored by Arpana Agrawal and Michael T. Lynskey of Washington University School of Medicine, with Alan J. Budney of the University of Arkansas for Medical Sciences.  “As many cannabis users smoke a mixture of cannabis and tobacco or chase cannabis use with tobacco, and as conditioned cues associated with smoking both substances may trigger use of either substance,” the researchers conclude, “a simultaneous cessation approach with cannabis and tobacco may be most beneficial.”

A blunt is simply a marijuana cigar, with the wrapping paper made of tobacco and the majority of loose tobacco removed and replaced with marijuana. In Europe, smokers commonly mix the two substances together and roll the combination into a single joint, the precise ratio of cannabis and nicotine varying with the desires of the user. “There is accumulating evidence that some mechanisms linking cannabis and tobacco use are distinct from those contributing to co-occurring use of drugs in general,” the investigators say. Or, as psychiatry postdoc Erica Peters of Yale put it in a press release, “There’s something about tobacco use that seems to worsen marijuana use in some way.” The researchers believe that this “something” involved may be a genetic predisposition. In addition to an overall genetic proclivity for addiction, do dual smokers inherit a specific propensity for smoked substances? We don’t know—but evidence is weak and contradictory so far.

Wouldn’t it be easier to quit just one drug, using the other as a crutch? The researchers don’t think so, and here’s why: In the few studies available, for every dually addicted participant who reported greater aggression, anger, and irritability with simultaneous cessation, “comparable numbers of participants rated withdrawal associated with dual abstinence as less severe than withdrawal from either drug alone.” So, for dual abusers, some of them may have better luck if they quit marijuana and cigarettes at the same time. The authors suggest that “absence of smoking cues when abstaining from both substances may reduce withdrawal severity in some individuals.” In other words, revisiting the route of administration, a.k.a. smoking, may trigger cravings for the drug you’re trying to quit. This form of “respiratory adaption” may work in other ways. For instance, the authors note that, “in addition to flavorants, cigarettes typically contain compounds (e.g. salicylates) that have anti-inflammatory and anesthetic effects which may facilitate cannabis inhalation.”

Studies of teens diagnosed with cannabis use disorder have shown that continued tobacco used is associated with a poor cannabis abstention rate. But there are fewer studies suggesting the reverse—that cigarette smokers fair poorly in quitting if they persist in cannabis use. No one really knows, and dual users will have to find out for themselves which categories seems to best suit them when it comes time to deal with quitting.

We will pass up the opportunity to examine the genetic research in detail. Suffice to say that while marijuana addiction probably has a genetic component like other addictions, genetic studies have not identified any gene variants as strong candidates thus far. The case is stronger for cigarettes, but to date no genetic mechanisms have been uncovered that definitively show a neurobiological pathway that directly connects the two addictions.

There are all sorts of environmental factors too, of course. Peer influences are often cited, but those influences often seem tautological: Drug-using teens are members of the drug-using teens group. Tobacco users report earlier opportunities to use cannabis, which might have an effect, if anybody knew how and why it happens.

Further complicating matters is the fact that withdrawal from nicotine and withdrawal from marijuana share a number of similarities.  The researchers state that “similar withdrawal syndromes, with many symptoms in common, may have important treatment implications.” As the authors sum it up, cannabis withdrawal consists of “anger, aggression or irritability, nervousness or anxiety, sleep difficulties, decreased appetite or weight loss, psychomotor agitation or restlessness, depressed mood, and less commonly, physical symptoms such as stomach pain and shakes/tremors.” Others complain of night sweats and temperature sensitivity.

And the symptoms of nicotine withdrawal? In essence, the same. The difference, say the authors, is that cannabis withdrawal tends to produce more irritability and decreased appetite, while tobacco withdrawal brings on an appetite increase and more immediate, sustained craving. Otherwise, the similarities far outnumber the differences.

None of this, however, has been reflected in the structure of treatment programs: “Emerging evidence suggests that dual abstinence may predict better cessation outcomes, yet empirically researched treatments tailored for co-occurring use are lacking.”

The truth is, we don’t really know for certain why many smokers prefer to consume tobacco and marijuana in combination. But we do know several reasons why it’s not a good idea. Many of the health-related harms are similar, and presumably cumulative: chronic bronchitis, wheezing, morning sputum, coughing—smokers know the drill. Another study cited by the authors found that dual smokers reported smoking as many cigarettes as those who only smoked tobacco. All of this can lead to “considerable elevation in odds of respiratory distress indicators and reduced lung functioning in those who used both.” However, there is no strong link at present between marijuana smoking and lung cancer.

Some researchers believe that receptor cross-talk allows cannabis to modify receptors for nicotine, or vice versa. Genes involved in drug metabolism might somehow predispose a subset of addicts to prefer smoking. But at present, there are no solid genetic or environmental influences consistent enough to account for a specific linkage between marijuana addiction and nicotine addiction, or a specific genetic proclivity for smoking as a means of drug administration.

Agrawal, A., Budney, A., & Lynskey, M. (2012). The Co-occurring Use and Misuse of Cannabis and Tobacco: A Review. Addiction DOI: 10.1111/j.1360-0443.2012.03837.x

Photo credit:

(First published at Addiction Inbox on March 22, 2012).

Monday, February 16, 2015

Troubling Link Between Shoplifting and Suicide

Compulsive theft can lead to tragic results.

In the fall of 2011, 71-year old Julia Grodinsky of London was convicted of shoplifting ornamental crystals and sentenced to 18 months of probation. What made the case unusual was that Grodinsky had been convicted of shoplifting 63 times over the past 60 years. It seems likely that the elderly thief will continue to steal, given her history of poor decision-making.

In The Republic, Plato asked whether thieves are made or born. It’s an excellent question. Kleptomania, as it is traditionally called, is a special class of theft behavior: a chronic condition marked by compulsive stealing, often committed by people who could easily afford to buy what they steal. Brian L. Odlaug, a visiting researcher with the faculty of health and medical sciences at the University of Copenhagen, believes that kleptomania’s primary feature is that it strikes "people who had a good marriage, nice home, great job—and yet could not stop from stealing inconsequential items." It is a rare disorder, he notes, “while sociopathy and theft for gain are quite common.”

Curiously, the stealing never seems to be about money: The most recent study measuring income and shoplifting shows that people in the United States with incomes over $70,000 shoplift 30 percent more than those earning less than $20,000 a year. Today, compulsive shoplifting is labeled in the DSM-IV as an impulse control disorder. But historically this controversial diagnosis was variously seen as a biological disorder brought on by female agitation in department stores, an expression of repressed Freudian sexual desire, or a socially constructed disease that blossomed as a reaction to modernity. (A modest majority of shoplifters are women). Some observers in the early 20th Century even described kleptomania as a clever trick by psychiatrists to worm their way into law courts as purveyors of expert testimony.

Researchers today are more likely to be interested in what researcher Jon E. Grant, professor of psychiatry and behavioral neuroscience at the University of Chicago’s Pritzker School of Medicine, calls the “neurocognitive sequelae of shoplifting.” Grant and Orlaug are part of a group of psychiatric researchers who have been studying compulsive shoplifting for more than a decade. In the Archives of Suicide Research, lead author Odlaug documented abnormally high suicide rates among a group of 107 participants with kleptomania, 24.3 percent of whom had reported at least one suicide attempt. That figure is “6 to 24 times higher than in the United States general population,” according to the report—roughly similar to the rate of suicide attempts among patients with schizophrenic disorders. It is higher than the rate of suicide attempts reported in cases of major depressive disorder (16.5 percent).

93 percent of the participants reported that their suicide attempt “was directly or indirectly due to their kleptomania symptoms (e.g., shame over the behavior; legal or personal problems resulting from shoplifting).” Believed to be the first attempt to survey the association between suicide and shoplifting, the study also teased out a strong association between bipolar spectrum disorder and kleptomania symptoms. The odds of a past suicide attempt were five times greater for kleptomania subjects who had also been diagnosed with bipolar disorder.

“The suicide data are very troubling,” says Grant. “No one screens for this behavior, or when they are told about, most clinicians are very dismissive of it. There is definitely an attitude about kleptomania that it is more of a criminal problem.”

Dr. Howard Shaffer, an associate professor at Harvard Medical School and director of the division on addiction at The Cambridge Health Alliance, who was not involved in the research, says that the work “seems a reasonable heads-up for clinicians to consider the role of impulsivity and its impact on suicidal ideation and behavior; kleptomania is one kind of proxy for impulsivity.”

Compulsive shoplifting is commonly associated with substance abuse, pathological gambling, personality disorders, and bipolar syndrome, while sometimes overlapping with other impulse control disorders. Does it share common neurobiological deficits with these conditions? In a report published in Comprehensive Psychiatry, Grant and co-workers recruited young adults with no history of substance abuse or recognized mental health disorders, and ran them through a barrage of psychological testing. For the investigators, the important question was whether compulsive stealing is associated with certain neuropsychological dysfunctions that make kleptomaniacs different from other people. As it turned out, people with kleptomania risked more points in a test called the Cambridge Gambling Task, with results “similar to previous reports in people with damage to the ventromedial prefrontal cortices.” It was an admittedly small study, but the researchers think the results show that shoplifting is not just a rash act, but one associated with “specific decision-making and working memory deficits.”

A small neuromaging study published by Grant in 2006 showed evidence of “compromised white matter microstructure in inferior frontal areas,” suggesting to Grant that the frontal parts of the brain involved in decision making “may not be as healthy.” For his part, Odlaug thinks this finding may help explain “why so many patients report an 'irresistible' impulse to steal and a failure to inhibit that impulse.” Odlaug cautions that while deficits of executive functioning appear to be involved, “I think it is far too early to suggest cognitive predictors of kleptomania or other disorders characterized by impulse control deficits.”

Neuroscientist Marc Lewis, professor of human development and applied psychology at Radboud University in Nijmegen, The Netherlands, and author of Memoirs of an Addicted Brain, also questions whether sufficient data existed for asserting a link between impulsive behavior and working memory deficits. However, Lewis agrees that kleptomania “is seemingly its own disorder,” and “overlaps only partially with other psychiatric categories.”

Can kleptomania be cured, or treated successfully? In 2009, in an article for Biological Psychiatry, Grant and colleagues recorded the results of their work with 25 patients with kleptomania who were given high doses of naltrexone, a drug that blocks opioid receptors and is used to treat alcoholism and heroin addiction. All of the participants had been arrested, and had spent at least one hour per week stealing. The 8-week study, believed to be the first placebo-controlled trial of a drug for the treatment of shoplifting, resulted in a remission of symptoms in two-thirds of those on naltrexone. Says Odlaug: “With such a dearth of treatment data available, naltrexone appears to be the first-line treatment at this time. We have found that naltrexone at slightly higher doses is beneficial for a number of folks with kleptomania.” Some researchers are also investigating use of cognitive behavioral therapies.

“Kleptomania is thought of as a behavioral addiction within addiction circles,” Odlaug adds, while conceding that not everyone agrees with the concept of addiction to behaviors rather than substances. The neuropsychological approach to uncontrollable shoplifting as by no means unanimous. Writing in Global Society, Thomas Lenz and Rachel MagShamhrain argue that kleptomania is an “invented disease,” coinciding with the rise of the department store and strong beliefs in feminine “hysteria.”

“I think the general view,” says Grant, “is that criminal issues, or potential criminal issues, are not as biological as, say, depression. It then becomes a vicious cycle, as lack of research then continues to justify why people say it is not really biological or psychological.”

Lamentably, the connection between bipolar syndrome and shoplifting did not become apparent until recently, because people with bipolar symptoms are routinely ruled out of clinical studies of impulse control disorders. “Screening for people with co-occurring bipolar affective disorder and kleptomania is extremely important,” Odlaug stresses. “Especially in psychiatric settings where kleptomania and other impulse control disorders often go unrecognized by clinicians.”

(By Dirk Hanson. Originally published February 11, 2013, by the Dana Foundation.)

Thursday, February 5, 2015

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 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, 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.