Mortality among users of marijuana, cocaine, amphetamine, ecstasy and opioids

May 2, 2011 11 comments

This post was chosen as an Editor's Selection for ResearchBlogging.orgWhile Illicit drugs have long been linked to higher mortality rates, the data is wildly variable.

In a paper recently published in the journal Drug and Alcohol Dependence, Danish researchers attempted to establish standard mortality ratios for the drugs cannabis, cocaine, amphetamine, MDMA (ecstasy) and opioids (e.g. heroin)*, while taking into consideration the effects of two intervening variables: drug injection with needles and psychiatric disorders (Is the mortality rate of cocaine users mediated by whether they have, for example, clinical depression?)

(*Individuals’ primary drug of choice)

The population they looked at included 20,581 people treated for drug abuse in Denmark over a 10-year period from 1996-2006. (These data are correlational and, therefore, the possibility of unidentified moderating variables exerting an effect on death rates is high.)

In brief, the results showed the following:

1. Those who injected drugs showed significantly higher mortality rates across the board. (This does conflict with past findings, which found no difference.)

2. Overall, psychiatric illness was not associated with higher mortality rates, with the exception of cocaine/amphetamine users, who, if they presented with psychiatric disorders, did show higher morality rates.

3. Pot smokers showed 5x increase in mortality rates (compared to the general population). Researchers suggest that increased mortality among pot smokers could be related to driving accidents, violent injuries and various other types of accidents. (a personal note: Based on my personal experience, this seems unlikely. Pot smokers tend to drive very conservatively (too slow, if anything!) and are famously not prone to violence.) What seems more likely to explain pot smokers’ higher mortality rate is that they are also using other drugs. Other studies have borne this out.

4. Cocaine and amphetamine users showed 6x death rates of the general population. Previous reports on stimulant abuse related deaths are highly variable. The variability is likely the result of other factors including physical conditions, HIV/AIDS, overdose, cardiovascular problems, injuries accidents, violent deaths and suicides.

5. Opiod users show increased mortality rates. Findings for both stimulants and opioids are in accordance with studies from other countries. Users of Heroin and other opioids showed by far the highest mortality rates of all drugs of abuse.

6. Ecstasy (MDMA) users did not show increased mortality rates. (However, it’s possible that a low number of deaths from MDMA contribute to low statistical power).

Conclusions that can be drawn from this report? Stay away from all drugs if you want to increase your chances of staying alive; but, especially, don’t do intravenous heroin. Psychiatric disorders plus drugs of abuse aren’t associated with increased mortality risks except for in the case of cocaine/amphetamine. Ecstasy is unlikely to kill you on its own, but that’s not to say it won’t do some long-term damage if abused. Although marijuana users showed higher mortality rates, there’s not good reason to believe this is solely the effect of marijuana, but other factors. Finally, the population under study here consisted of people seeking treatment, so it’s unknown if this represents the drug using population as a whole.

I think it’s pretty clear, given the number of questions and unknowns this study presents, that there is a lot more to learn about drug-related mortality risk.

References
Arendt M, Munk-Jørgensen P, Sher L, & Jensen SO (2011). Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: a nationwide follow-up study of Danish substance users in treatment. Drug and alcohol dependence, 114 (2-3), 134-9 PMID: 20971585

Categories: Drugs Tags: , , ,

The Neural Correlates of Romantic Love

May 1, 2011 Leave a comment


ResearchBlogging.org

For the most part, fMRI studies attempt to localize cognitive processes to specific regions in the brain. Popular media often introduce these studies with headlines that tout the discovery of “the brain region” for memory, language, empathy, moral reasoning, loving weiner schnitzel and so on.

These headlines can be terribly misleading, as they’re often misinterpreted to suggest a specific brain region is dedicated to a single function, when, in fact, any given function maps on to a network of regions (forming a circuit), while any given region is part of multiple circuits subserving many functions. Similar faux pas can be found in descriptions of the functions associated with genes, e.g. “The gene for (fill in the blank).”

A few years back, the NY Times ran an infamous piece featuring the work of a neuromarketing company. In a horrible experiment fit for The Onion, participants lay in the scanner while looking at pictures of then presidential candidates. Subjects showed increased amygdala activation to pictures of Mitt Romney, which researchers interpreted as a sign of anxiety.

But after watching Romney speak on video, the amygdala activity died down, which researchers said showed that voters’ anxiety had decreased.

Meanwhile subjects’ anterior cingulates lit up to pictures of Hillary Clinton.

Here’s how researchers interpreted this neural activity:

Emotions about Hillary Clinton are mixed. Voters who rated Mrs. Clinton unfavorably on their questionnaire appeared not entirely comfortable with their assessment. When viewing images of her, these voters exhibited significant activity in the anterior cingulate cortex, an emotional center of the brain that is aroused when a person feels compelled to act in two different ways but must choose one. It looked as if they were battling unacknowledged impulses to like Mrs. Clinton.

The Times article about the “research” was quickly and roundly criticized by prominent neuroscientists, 17 of whom quickly responded with a signed letter to the editor, which the Times ran a couple of days later:

To the Editor:

“This Is Your Brain on Politics” (Op-Ed, Nov. 11) used the results of a brain imaging study to draw conclusions about the current state of the American electorate. The article claimed that it is possible to directly read the minds of potential voters by looking at their brain activity while they viewed presidential candidates.

For example, activity in the amygdala in response to viewing one candidate was argued to reflect “anxiety” about the candidate, whereas activity in other areas was argued to indicate “feeling connected.” While such reasoning appears compelling on its face, it is scientifically unfounded.

As cognitive neuroscientists who use the same brain imaging technology, we know that it is not possible to definitively determine whether a person is anxious or feeling connected simply by looking at activity in a particular brain region. This is so because brain regions are typically engaged by many mental states, and thus a one-to-one mapping between a brain region and a mental state is not possible.As cognitive neuroscientists, we are very excited about the potential use of brain imaging techniques to better understand the psychology of political decisions. But we are distressed by the publication of research in the press that has not undergone peer review, and that uses flawed reasoning to draw unfounded conclusions about topics as important as the presidential election.

Adam Aron, Ph.D., University of California, San Diego
David Badre, Ph.D., Brown University
Matthew Brett, M.D., University of Cambridge
John Cacioppo, Ph.D., University of Chicago
Chris Chambers, Ph.D., University College London
Roshan Cools, Ph.D., Radboud University, Netherlands
Steve Engel, Ph.D., University of Minnesota
Mark D’Esposito, M.D., University of California, Berkeley
Chris Frith, Ph.D., University College London
Eddie Harmon-Jones, Ph.D., Texas A&M University
John Jonides, Ph.D., University of Michigan
Brian Knutson, Ph.D., Stanford University
Liz Phelps, Ph.D., New York University
Russell Poldrack, Ph.D., University of California, Los Angeles
Tor Wager, Ph.D., Columbia University
Anthony Wagner, Ph.D., Stanford University
Piotr Winkielman, Ph.D., University of California, San Diego

Undoubtedly, fewer people saw that letter than saw the original article, which was much more prominently displayed.

(By the above study’s logic, looking at a picture of Donald Trump should elicit activity in the anterior insula, a region often associated with disgust responses)

It’s unfortunate that the study received such a prominent platform for distribution because people, especially non scientists, can be heavily influenced by articles with pictures of brains or technical sounding neuro language. One study, which I’ve written about on the blog, found that people were much more likely to believe a nonsensical article if it had meaningless neuroscience language in it than if it didn’t. As the average lay person doesn’t possess the technical skills to distinguish between valid and invalid fMRI studies, it’s up to the scientific community to police itself, which it does a pretty good job of through the peer review process.

This next study I’ll talk about demonstrates some of the challenges inherent to mapping localized neural activity onto unseen mental processes; in this case, the subjective experience of intense, romantic long-term love.

Aaron and colleagues previously published a study that presented neural correlates of intense romantic love (2005). In brief, the study reported that regions in the reward circuit of the brain were activated in response to pictures of a lover (versus a close friend). In the current study, they wanted to explore if these findings could be extended to long-term married couples (couples together for more than 20+ years who report still being madly in love).

Participants lay in the scanner and were repeatedly presented with pictures from four different categories: their partner, a close friend, and both a highly familiar and low-familiar neutral acquaintance. They were instructed to think about “experiences with each stimulus person (that were) nonsexual in nature.”

The fMRI data was analyzed via subtraction, a common fMRI analysis method in which one condition is compared to another to see if any differences fall out. The contrast of interest was between the partner and the close friend. In a cognitive process sense, the only difference thought to exist between perceiving these two individuals was thought to be the subject’s romantic love for one and not for the other. So if neural activity in the close friend condition is subtracted from activity in the partner condition, whatever is left over should represent the neural substrate of romantic love.

Researchers found activation in the ventral tegmental area, substantia nigra and nucleus accumbens (and the hippocampus, which corresponded with reported sex frequency, but the effect seems to be driven largely by two outliers, one of whom reported they have sex almost every day).

The activity does suggest a classic reward response and replicates previous findings. However, the big question isn’t whether there is a response, but rather what’s driving it?

A valid fMRI study doesn’t only rely on the integrity or analysis of the fMRI data, but, also, and perhaps more importantly, on the experimental design. In order to attribute increased activation in one condition versus the other to a specific cognitive function, one must be confident they have created conditions that have cleanly isolated the independent variable of interest (romantic love). The ventral tegmental area and other regions in the basal ganglia have been repeatedly shown to encode reward value – that is, they respond to things that give us hedonic pleasure, such as food, drugs, sex or receiving money. Past work has shown that intense romantic love is associated with activity in the those regions (Aaron 2005). In the current study, activity in some neural regions previously associated with maternal pair bonding was shown (substantia nigra, for one). The authors hypothesized that neural correlates for romantic long-term love should encompass those associated with both intense romantic love and maternal pair bonding.

But this analysis is dependent on long-term, romantic love being the only difference between conditions that would explain the differences in brain activity. And that may not entirely be the case.

Alternative Explanations
Just to refresh, the major dependent measure of interest was neural activity, especially of reward circuitry, while subjects looked at pictures of their long-term partner versus a close friend. One additional difference between these conditions (beyond romantic love) is that romantic partners are probably more familiar and closer to participants than close friends. This is a shortcoming acknowledged by the authors.

This difference suggests a causal chain of cognitive operations that could offer alternative explanations for some of the data seen in this study. First, It’s been shown that we prefer things that are familiar to us (the “mere exposure” effect, Zajonc, 1968). Second, we’re able to process familiar things (or people) much more fluently compared to the less familiar (Reber). Third, fluency processing has been associated with judgments of aesthetic appreciation such that the more fluently we can process something, the more beautiful or attractive we’re likely to rate it (Alter). Although the objective attractiveness of the photos was controlled for via a group of independent raters, the participants were likely much more subjective in their judgments and perhaps found their partners more attractive than an objective viewer might. Viewing attractive faces has been shown to elicit strong neural activity, particularly in the reward circuitry (NaCC and OFC).

Furthermore, it has been posited that people incorporate close others into their psychological construct of self. Recent studies (deGreck 2008) showed that regions active in a reward task, such as the bilateral ventral striatum, and the ventral tegmental area (VTA), are also involved in differentiating between high and low personal relevance.It seems that we find thinking about ourselves pretty damn rewarding! (We’re all at least a little bit narcissistic). To the extent that someone has been incorporated into our self concept, thinking about that person, or looking at their picture as in this study, could be correlated with responses in reward regions of the brain in part because they activate thoughts of ourselves.

Both the familiarity –> processing fluency –> attractiveness model and self relevant thinking are plausible alternative explanations for at least some of the neural correlates found in this paper.

One other potential area of concern is that there is no way of knowing that participants weren’t thinking about sex with their partners, even though they were told not to. This might be especially difficult to achieve, especially for the two outliers who reported almost daily sex. Regions active during sexual arousal include R. amygdala, hypothalamus, hippocampus, midbrain, mOFC and nucleus accumbens, many of which were found to be active in this study.

The neural activity measured here may very well reflect some aspect of individuals’ love for their partners. But there seem to be other possible explanations for some of the data. I suppose that’s why people call the study of consciousness, of which subjective experiences such as romantic love are a subset, the “hard problem.”

References
Acevedo BP, Aron A, Fisher HE, & Brown LL (2011). Neural correlates of long-term intense romantic love. Social cognitive and affective neuroscience PMID: 21208991

Aron, A., Fisher, H., Mashek, D., Strong, G., Li, H., Brown, L. (2005). Reward, motivation and emotion systems associated with early-stage intense romantic love. Journal of Neurophysiology, 93, 327–37.

DEGRECK, M., ROTTE, M., PAUS, R., MORITZ, D., THIEMANN, R., PROESCH, U., BRUER, U., MOERTH, S., TEMPELMANN, C., & BOGERTS, B. (2008). Is our self based on reward? Self-relatedness recruits neural activity in the reward system NeuroImage, 39 (4), 2066-2075 DOI: 10.1016/j.neuroimage.2007.11.006

Alter, A., & Oppenheimer, D. (2008). Easy on the mind, easy on the wallet: The roles of familiarity and processing fluency in valuation judgments Psychonomic Bulletin & Review, 15 (5), 985-990 DOI: 10.3758/PBR.15.5.985

Peskin, M., & Newell, F. (2004). Familiarity breeds attraction: Effects of exposure on the attractiveness of typical and distinctive faces Perception, 33 (2), 147-157 DOI: 10.1068/p5028

Reber, R., Schwarz, N., & Winkielman, P. (2004). Processing Fluency and Aesthetic Pleasure: Is Beauty in the Perceiver’s Processing Experience? Personality and Social Psychology Review, 8 (4), 364-382 DOI: 10.1207/s15327957pspr0804_3

Name games

April 26, 2011 Leave a comment

Research has shown that people’s names influence what professions they choose to enter; for example, men named Dennis are overrepresented among dentists and men named Raymond are overrepresented among doctors who specialize in radiology.

I wonder if guilt about his name is what drove the third author below to study the ill effects of cigarette smoking …


Unconscious priming studies (for adults only)

April 25, 2011 Leave a comment

The last few years have seen a calvacade of studies demonstrating that unexpected elements in the environment can unconsciously prime attitudes, beliefs and behaviors.

Just a few recent examples:

1. People are more likely to judge a person as “warmer” just after holding a warm (compared to a cold) cup (Williams & Bargh 2008a):
2. Job candidates whose resumes were seen on a heavy (versus light) clipboard were rated as better qualified for a job (Ackerman 2010)
3. The hotter the temperature is in a room or outside, the more likely people are to believe in global warming (Li 2011)
4. Working on a jigsaw puzzle with rough (versus smooth) pieces made people rate a subsequent personal encounter as “less smooth” (Ackerman 2010)

Based on the abundance of findings, there seems to be a robust market in unconscious priming.

Why do we see these kinds of effects? Yale psychologist and implicit cognition guru John Bargh said “… these (kinds of) demonstrations suggest a cognitive architecture in which social psychological concepts metaphorically related to physical-sensory concepts … are grounded in those physical concepts, such that activation of the physical version also activates (primes) the more abstract psychological concept.” What he’s describing is essentially conceptual metaphor theory, which originated with George Lakoff and Mark Johnson in the early 1980s. The theory suggests that cognition is largely based on metaphoric thinking, whereby the structure and logical protocols of one domain guides or structures thinking in another.

Aside from their theoretical contributions, these kinds of studies also provide a certain entertainment value in that they demonstrate associations between a given stimuli and an attitude or behavior that confounds our expectations.

A new study from University of New Mexico researchers presents yet another priming effect that can be added to the ever growing list. But this one ain’t for the kiddies.

In a nutshell: The study showed that the smell of poop, er, uh, fecal matter, (delivered in the form of a spray from a bottle of “Liquid Ass,” a novelty odor liquid) made participants more likely to report their intentions to use condoms in the near future. In other words, the smell of feces motivated safe sex attitudes. Although unpleasant to describe and probably even more so to have carried out, it does fit theoretically with a literature showing that pathogen avoidance/visceral disgust response can function as a mechanism to elicit unexpected effects on seemingly unrelated behaviors and attitudes. I recently discussed a study that looked at the flip side of the same coin. In this study, priming concerns about cleanliness made participants more likely to condemn a slightly immoral sex act and more likely to report conservative political attitudes (Subjects in the experimental condition were standing next to a soap dispenser).

While credit certainly has to be given for being able to work “Liquid Ass” into an experiment, I’m not sure that the researchers have shown pathogen-avoidance concern is the mechanism motivating subjects’ change in attitude.

For one, sufficient control questionnaires don’t seem to have been employed, asking participants to report attitudes in domains other than those in which pathogen avoidance plays a role. Perhaps the nasty scent mediated a more general shift in risk taking or impulsivity. Furthermore, self report is notoriously unreliable at predicting behavior; that is, participants’ answers might in part reflect self presentation concerns as much as shifts in attitude that would result in behavioral change. Finally, it’s possible that the general unpleasantness of the stimuli caused the shift in attitude and not it’s viscerally disgusting nature. One possible control could be an additional condition with an unpleasant, non-pathogen avoidance related stimuli from a different domain (e.g., an unpleasant noise).

Although it would be interesting to see if the effects would still hold up to these slight modifications, I don’t think I would want to be the one to run it…

References
Anderson ML (2010). Neural reuse: a fundamental organizational principle of the brain. The Behavioral and brain sciences, 33 (4) PMID: 20964882

Tybur JM, Bryan AD, Magnan RE, & Hooper AE (2011). Smells like safe sex: olfactory pathogen primes increase intentions to use condoms. Psychological science : a journal of the American Psychological Society / APS, 22 (4), 478-80 PMID: 21350181

Ackerman, J., Nocera, C., & Bargh, J. (2010). Incidental Haptic Sensations Influence Social Judgments and Decisions Science, 328 (5986), 1712-1715 DOI: 10.1126/science.1189993

Li Y, Johnson EJ, & Zaval L (2011). Local warming: daily temperature change influences belief in global warming. Psychological science : a journal of the American Psychological Society / APS, 22 (4), 454-9 PMID: 21372325

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Scientists and journalists convene to discuss blogs and whatnot

April 23, 2011 Leave a comment

A couple of nights back, I attended a panel discussion at Rockefeller University in NYC, organized by SONYC and sponsored by Nature. Entitled Courting Controversy : how to successfully engage an online audience with complex or controversial topics, The meeting consisted of a three person panel, a climate scientist, a pediatric clinician and a former science journalist, addressing a crowd full of journalists and scientists. I won’t give a full review but just a couple of quick points.

One question that emerged from the meeting was whether or not the role of scientist bloggers and/or science journalists should be to educate their readers. The consensus that emerged from the panel seemed to be that education should not be a goal. One panelist, Gavin Schmidt, a climate researcher at NASA’s Goddard Institute for Space Studies and a driving force behind the RealClimate blog, made mention of how scientists live in the space between the known and the unknown, and that in order to really understand discoveries that emerge from this space in a given field, one would need an extensive background education, e.g. the kind of background that one receives when doing a PhD. This kind of education, Schmidt said takes many thousands of hours and can’t very well be accomplished through reading blogs or articles in mainstream media.

While this is certainly true, I’m not sure that science writers are not educating their readers. It’s perhaps a question of how you define “educate”. It might be defined as an act by which one is, “qualified or trained for a particular calling, practice, or trade.” By that definition, any given piece of science writing would certainly not qualify. But, education can also be defined, more simply, as the act of providing something of informational value. Science writers certainly do that. And to the extent that a person’s opinion is influenced by information they’ve consumed, whatever the format, then I think we can say some educating has taken place.

One other point that stuck with me was made by David Ropeik, a former journalist who runs the blog, On Risk. He made the point that negative messages carry much more weight than positive messages. Not a new observation, to be sure, but it’s good to be reminded that to participate in the news/information space is to be in competition for reader’s eyeballs. How one frames their message is probably as important as the message itself. The “competition” probably has less scruples than you. Negative sells. One ignores this maxim at their own peril.

There was some good vigorous discussion in the latter part of the event and the whole thing should be online soon.

Protected: The case of the man who couldn’t find the beat

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Smoking makes impulsive teen rats even more impulsive

April 18, 2011 2 comments

It’s one of the truisms of human life that teenagers often do silly, stupid and/or dangerous things. We certainly don’t need science to tell us that. One reason this seems to be the case is that, on average, teens have trouble optimally weighing risk vs. reward. I’m not excluding myself from this characterization. In fact, I sometimes marvel that I survived my teen years intact, if at all.

One stupid thing I and many of my friends did as teenagers was to try smoking.

There are no rational arguments in favor of smoking. Yet, according to one study, most adult smokers start before age 19 and 70% of all adolescents report trying a cigarette at least once. Messages directed to adolescents and teens against smoking often fall on flat ears. In addition to subpar decision making skills, many teens hold the advice of their elders in low regard and are apt to pick up a cigarette as an act of defiance or as a show of their burgeoning adulthood. Hollywood films certainly contribute to the smoking mythology through their noble portrayals of troubled, rebellious or misunderstood teens reaching for smokes when the chips are down.

Although the health risks associated with smoking are widely known, a recent Nature Neuroscience study has provided even more reasons for teens to avoid smoking. Researchers from the Netherlands found that in adolescent rats, exposure to smoking led to increased and long lasting impulsiveness and impaired measures of attention in adulthood. In contrast, adult animals exposed to similar levels of nicotine did not show these long term effects. So, the impulsiveness that might lead a teen to try smoking could be increased by the very product of that impulsiveness, creating a vicious feedback cycle. Nasty business.

What’s the molecular mechanism? A proteomic analysis of 297 different mPFC proteins in adolescent rats who had exposure to smoking showed that levels of mGLuR2 was downregulated. mGluR2 is a metabotropic glutamatergic receptor that sits on the presynaptic side of synapses in the mPFC, a brain region important for cognitive control and attention. Adolescent nicotine exposure resulted in decreased mGLuR2 signaling and reduced plasticity in the mPFC. This was shown to be directly related to attentional deficits by a rescue experiment in which a glutamate agonist was injected into the mPFC in vivo. The agonist restored attentional performance to normal levels but didn’t affect impulsiveness.

In sum, the adolescent brain is more susceptible to the consequences of smoking via alteration of synaptic mGluR2 protein levels. It’s known that nicotine exerts its initial effects on the brain through nicotinic acetylcholine receptor activation and this study suggests that adolescents are uniquely vulnerable to increased activation of these receptors.

The researchers acknowledge that the sequence of molecular events is unknown, but speculate that “…mGluR2 levels following nicotine exposure at the end of adolescence compensate for nicotine’s actions and inhibit neurotransmitter release.” One caveat to keep in mind is that it’s unknown the extent to which this effect would be replicated in humans. Another important point is that in this experiment, nicotine was dissolved in solution and administered subcutaneously. Cigarettes contain many other carcinogens and toxins to which adolescents could be particularly vulnerable, so the long-term cognitive effects of cigarette smoking could extend far beyond those uncovered in this study, which looked just at nicotine.

The takeaway message is definitely clear: Parents, do everything you can to keep your kids from smoking!*

*I’m an advocate for making the sale of tobacco and tobacco related products illegal. Tobacco offers no clear benefits to society, with the exception of a few thousand jobs and the enrichment of a couple handfuls of business executives, while incurring great economic costs to the nation as a whole. Although nicotine has shown some cognitive benefits to individuals in certain disease states, all in all its mostly detrimental. (I’m a member of that most annoyingly vociferous group of anti-smoking activists: ex-smokers. Maybe we’re so adamant because we know how hard it is to quit!) That long-term cognitive deficits are now being shown to accrue in cigarette smoking teens is hopefully another nail in the coffin of the tobacco industry and smoking culture in general, which will perhaps be looked back upon as a sign of the special ignorance of our times.

References

Counotte DS, Goriounova NA, Li KW, Loos M, van der Schors RC, Schetters D, Schoffelmeer AN, Smit AB, Mansvelder HD, Pattij T, & Spijker S (2011). Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence. Nature neuroscience, 14 (4), 417-9 PMID: 21336271

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