Will Power and Its Limits

How to strengthen your self-control.

Reason in man obscured, or not obeyed,
Immediately inordinate desires,
And upstart passions, catch the government
From reason; and to servitude reduce
Man, till then free.
—John Milton, Paradise Lost

What is will power? Is it the same as delayed gratification? Why is will power “far from bulletproof,” as researchers put it in a recent article for Neuron? Why is willpower “less successful during ‘hot’ emotional states”? And why do people “ration their access to ‘vices’ like cigarettes and junk foods by purchasing them in smaller quantities,” despite the fact that it’s cheaper to buy in bulk?

 Everyone, from children to grandparents, can be lured by the pull of immediate gratification, at the expense of large—but delayed—rewards. By means of a process known as temporal discounting, the subjective value of a reward declines as the delay to its receipt increases. Rational Man, Economic Man, shouldn’t behave in a manner clearly contrary to his or her own best interest. However, as Crockett et. al. point out in a recent paper in Neuron “struggles with self-control pervade daily life and characterize an array of dysfunctional behaviors, including addiction, overeating, overspending, and procrastination.”

Previous research has focused primarily on “the effortful inhibition of impulses” known as will power. Crockett and coworkers wanted to investigate another means by which people resist temptations. This alternative self-control strategy is called precommitment, “in which people anticipate self-control failures and prospectively restrict their access to temptations.” Good examples of this approach include avoiding the purchase of unhealthy foods so that they don’t constitute a short-term temptation at home, and putting money in financial accounts featuring steep penalties for early withdrawal. These strategies are commonplace, and that’s because people generally understand that will power is far from foolproof against short-term temptation. People adopt strategies, like precommitment, precisely because they are anticipating the possibility of a failure of self-control. We talk a good game about will power and self-control in addiction treatment, but the truth is, nobody really trusts it—and for good reason.  The person who still trusts will power has not been sufficiently tempted.

The researchers were looking for the neural mechanisms that underlie precommitment, so that they could compare them with brain scans of people exercising simple self-control in the face of short-term temptation.

After behavioral and fMRI testing, the investigators used preselected erotic imagery rated by subjects as either less desirable ( smaller-sooner reward, or SS), or more highly desirable ( larger-later reward, or LL). The protocol is complicated, and the analysis of brain scans is inherently controversial. But previous studies have shown heightened activity in three brain areas when subjects are engaged in “effortful inhibition of impulses.” These are the dorsolateral prefrontal cortex (DLPFC), the inferior frontal gyrus (IFG), and the posterior parietal cortex (PPC). But when presented with opportunities to precommit by making a binding choice that eliminated short-term temptation, activity increased in a brain region known as the lateral frontopolar cortex (LFPC).  Study participants who scored high on impulsivity tests were inclined to precommit to the binding choice.

In that sense, impulsivity can be defined as the abrupt breakdown of will power. Activity in the LFPC has been associated with value-based decision-making and counterfactual thinking. LFPC activity barely rose above zero when subjects actively resisted a short-term temptation using will power.  Subjects who chose the option to precommit, who were sensitive to the opportunity to make binding choices about the picture they most wanted to see, showed significant activity in the LFPC. “Participants were less likely to receive large delayed reward when they had to actively resist smaller-sooner reward, compared to when they could precommit to choosing the larger reward before being exposed to temptation.”

Here is how it looks to Molly Crockett and her fellow authors of the Neuron article:

Precommitment is adaptive when willpower failures are expected…. One computationally plausible neural mechanism is a hierarchical model of self-control in which an anatomically distinct network monitors the integrity of will-power processes and implements precommitment decisions by controlling activity in those same regions. The lateral frontopolar cortex (LFPC) is a strong candidate for serving this role.

None of the three brain regions implicated in the act of will power were active when opportunities to precommit were presented.  Precommitment, the authors conclude, “may involve recognizing, based on past experience, that future self-control failures are likely if temptations are present. Previous studies of the LFPC suggest that this region specifically plays a role in comparing alternative courses of action with potentially different expected values.” Precommitment, then, may arise as an alternative strategy; a byproduct of learning and memory related to experiences “about one’s own self-control abilities.”

There are plenty of caveats for this study: A small number of participants, the use of pictorial temptations, and the short time span for precommitment decisions, compared to real-world scenarios where delays to greater rewards can take weeks or months. But clearly something in us often knows that, in the immortal words of Carrie Fisher, “instant gratification takes too long.” For this unlucky subset, precommitment may be a vitally important cognitive strategy. “Humans may be woefully vulnerable to self-control failures,” the authors conclude, “but thankfully, we are sometimes sufficiently far-sighted to circumvent our inevitable shortcomings.” We learn—some of us—not to put ourselves in the path of temptation so readily.

Crockett M., Braams B., Clark L., Tobler P., Robbins T. & Kalenscher T. (2013). Restricting Temptations: Neural Mechanisms of Precommitment, Neuron, 79 (2) 391-401. DOI: 10.1016/j.neuron.2013.05.028

Photo Credit: http://tommyboland.com/2011/05/27/white-knuckle-living/

Peyote and the White Man’s Gin

Aldous Huxley reflects on drugs in 1958.

In the Brave New World of my fable there was no whisky, no tobacco, no illicit heroin, no bootlegged co­caine. People neither smoked, nor drank, nor sniffed, nor gave themselves injections. Whenever anyone felt depressed or below par, he would swallow a tablet or two of a chemical compound called soma....

In small doses it brought a sense of bliss, in larger doses it made you see visions and, if you took three tablets, you would sink in a few minutes into refreshing sleep. And all at no physiologi­cal or mental cost. The Brave New Worlders could take holidays from their black moods, or from the familiar annoyances of everyday life, without sacrificing their health or permanently reducing their efficiency....

But this most precious of the subjects' inalienable privileges was at the same time one of the most powerful instruments of rule in the dictator's armory. The systematic drugging of individuals for the benefit of the State (and inciden­tally, of course, for their own delight) was a main plank in the policy of the World Controllers. The daily soma ration was an insurance against personal malad­justment, social unrest and the spread of subversive ideas....

For example, the classical tranquillizer is opium. But opium is a dangerous drug which, from neolithic times down to the present day, has been making addicts and ruining health. The same is true of the classical euphoric, alco­hol -- the drug which, in the words of the Psalmist, "maketh glad the heart of man." But unfortunately alcohol not only maketh glad the heart of man; it also, in excessive doses, causes illness and addiction, and has been a main source, for the last eight or ten thou­sand years, of crime, domestic unhappiness, moral deg­radation and avoidable accidents....

Among the classical stimulants, tea, coffee and maté are, thank goodness, almost completely harmless. They are also very weak stimulants. Unlike these "cups that cheer but not inebriate," cocaine is a very powerful and a very dangerous drug. Those who make use of it must pay for their ecstasies, their sense of unlimited physical and mental power, by spells of agonizing depression, by such horrible physical symptoms as the sensation of being infested by myriads of crawling insects and by paranoid delusions that may lead to crimes of violence. Another stimulant of more recent vintage is amphetamine, better known under its trade name of Benzedrine. Amphetamine works very effec­tively -- but works, if abused, at the expense of mental and physical health. It has been reported that, in Ja­pan, there are now about one million amphetamine ad­dicts....

Of the classical vision-producers the best known are the peyote of Mexico and the southwestern United States and Cannabis sativa, consumed all over the world under such names as hashish, bhang, kif and marihuana. According to the best medical and anthro­pological evidence, peyote is far less harmful than the White Man's gin or whisky.

--From Aldous Huxley’s essay, "Chemical Persuasion," which appeared in Brave New World Revisited. Also cited in Moksha by Michael Horowitz and Cynthia Palmer.

Photo credit: http://therevealer.org 

Methamphetamine: An Excerpt

There’s more than one kind of monster.

Type and I pass the pipe.  The overhead light flickers and the wind picks up even more. It’s coming from the north because with each exhale, the smoke slips past my face, back toward the Twin Cities and my dead parents.
 
But for a brief moment, I’m not thinking about all that. I’m feeling the closest thing I can think of to God and he’s playing the samba inside of my body, his fingers gentle, as they press on the backs of my retinas, my spine, the tendons along my hip flexors. I’m thinking that I love drugs more than anything. That they are the one and only constant in my life. Yeah, they demand a lot of attention and effort, but their love is legendary, their compassion endless. I hold each hit for hours, exhale for decades. The determination that comes with the onset of a high rushes back and I’m all about conquering the world and making money and finding happiness in the form of a loving woman who knows when it’s time to brush the backs of her nails across my cheek and then I’m thinking about this being the same thing as what God is doing to me now.

I love it when my heart rattles against my uvula.

I love it when my vision is a camera shutter.

I love it when I know that someday, I will do great things.

I love it when methamphetamines make things okay.

But I don’t love it when I start to hallucinate because the line between knowing it’s only the drugs and knowing your psyche is about to snap the fuck apart like a high wire is oh so delicate....

—From Fiend, a novel by Peter Stenson

From “The Pleasures and Pains of Coffee”

By Honore de Balzac, translated by Robert Onopa.

Coffee is a great power in my life; I have observed its effects on an epic scale….

Coffee affects the diaphragm and the plexus of the stomach, from which it reaches the brain by barely perceptible radiations that escape complete analysis; that aside, we may surmise that our primary nervous flux conducts an electricity emitted by coffee when we drink it. Coffee's power changes over time. [Italian composer Gioacchino] Rossini has personally experienced some of these effects as, of course, have I. "Coffee," Rossini told me, "is an affair of fifteen or twenty days; just the right amount of time, fortunately, to write an opera." This is true. But the length of time during which one can enjoy the benefits of coffee can be extended.

For a while - for a week or two at most - you can obtain the right amount of stimulation with one, then two cups of coffee brewed from beans that have been crushed with gradually increasing force and infused with hot water.

For another week, by decreasing the amount of water used, by pulverizing the coffee even more finely, and by infusing the grounds with cold water, you can continue to obtain the same cerebral power.

When you have produced the finest grind with the least water possible, you double the dose by drinking two cups at a time; particularly vigorous constitutions can tolerate three cups. In this manner one can continue working for several more days....

Finally, I have discovered a horrible, rather brutal method that I recommend only to men of excessive vigor... It is a question of using finely pulverized, dense coffee, cold and anhydrous, consumed on an empty stomach. This coffee falls into your stomach, a sack whose velvety interior is lined with tapestries of suckers and papillae. The coffee finds nothing else in the sack, and so it attacks these delicate and voluptuous linings; it acts like a food and demands digestive juices; it wrings and twists the stomach for these juices, appealing as a pythoness appeals to her god; it brutalizes these beautiful stomach linings as a wagon master abuses ponies; the plexus becomes inflamed; sparks shoot all the way up to the brain. From that moment on, everything becomes agitated. Ideas quick-march into motion like battalions of a grand army to its legendary fighting ground, and the battle rages. Memories charge in, bright flags on high; the cavalry of metaphor deploys with a magnificent gallop; the artillery of logic rushes up with clattering wagons and cartridges; on imagination's orders, sharpshooters sight and fire; forms and shapes and characters rear up; the paper is spread with ink - for the nightly labor begins and ends with torrents of this black water, as a battle opens and concludes with black powder.

I recommended this way of drinking coffee to a friend of mine, who absolutely wanted to finish a job promised for the next day: he thought he'd been poisoned and took to his bed, which he guarded like a married man. He was tall, blond, slender and had thinning hair; he apparently had a stomach of papier-mache. There has been, on my part, a failure of observation…."

Crack Babies Are Turning Out Okay

Major study concludes that crack panic was overblown.

In an excellent story for the Philadelphia Inquirer, Susan FitzGerald traces the fortunes of Philadelphia children enrolled in a study that began in 1989, at the height of the crack “epidemic” in the U.S. Headed up by Hallam Hurt, then the chair of neonatology at Albert Einstein Medical Center, a group began the in-vitro study of babies exposed to maternal crack cocaine use. One of the longest-running studies of its kind, the NIDA-funded research on 224 babies born between 1989 and 1992, half of them cocaine-exposed, the other half normal controls, was now coming to a close. And the results were not what most people were expecting.

In the Inquirer article, Hurt notes that cocaine can in fact trigger premature labor, raise blood pressure, and risk a condition in which the placenta breaks loose from the uterine wall. So it was natural to go looking for long-term effects in all of those twitching, underweight newborn crack babies viewers  saw on television. Physicians warned that damage to developing dopamine systems would result in long-term or permanent impairments in attention, language, and memory. So Hurt and colleagues went looking—and couldn’t find them. Neither could researchers at other institutions.  Said Hurt: “We began to ask, ‘Was there something else going on?’”

As FitzGerald writes: “The years of tracking kids have led Hurt to a conclusion she didn’t see coming. ‘Poverty is a more powerful influence on the outcome of inner-city children than gestational exposure to cocaine,'" Hurt said.  For example, babies born to mothers on heroin or methadone will have certain characteristic withdrawal symptoms, which can be managed by informed hospital staff. The same is true with newborns whose mothers have been using crack. In most cases, these withdrawals can be managed without permanent harm to the infant.

In a paper authored by Hurt, Laura M Betancourt, and others, the investigators write: “It is now well established that gestational cocaine exposure has not produced the profound deficits anticipated in the 1980s and 1990s, with children described variably as joyless, microcephalic, or unmanageable.” The authors do not rule out “subtle deficits,” but do not find evidence for them in functional outcomes like school or transition to adulthood.

How did this urban legend get started? In the 1980s, during the Reagan-Bush years, Americans were confronted with yet another drug “epidemic.” The resulting media fixation on crack provided a fascinating look at what has been called “drug education abuse.” This new drug war took off in earnest after Congress and the media discovered that an inexpensive, smokable form of cocaine was appearing in prodigious quantities in some of America’s larger cities. Crack was a refinement to freebasing, and a drug dealer’s dream. The “rush” from smoking crack was more potent, but even more transient, than the short-lived high from nasal ingestion.

Coupled with this development were the cocaine-related deaths of two well-known athletes, college basketball star Len Bias and defensive back Don Rogers of the Cleveland Browns. Bias played for Maryland, a home team in Washington, D.C. Six months earlier, Reagan had brought the military into the drug wars in a major way. The initial test of the directive was Operation Blast Furnace, a no-holds-barred attack on cocaine laboratories in the jungles of Bolivia.

As I wrote in 2008 in The Chemical Carousel:

The death of Len Bias elevated cocaine paranoia to the realm of the mythic. Cocaine became America’s first living-room drug, courtesy of the nightly news. The summer of 1986 will be remembered as the season of the “crack plague,” as viewers were bombarded with long news stories and specials. NBC Nightly News offered a special report on crack, during which a correspondent told viewers:  “Crack has become America’s drug of choice... it’s flooding America....”

The hyperkinetic level of television coverage ultimately led TV Guide Magazine to commission a report from the News Study Group, headed by Edwin Diamond at New York University. The investigators quickly demolished the notion that cocaine had become America’s “drug of choice,” and were at a loss to account for where the networks had come up with it:  “Statistically, alcohol and tobacco are the legal ‘drugs of choice’:  53 million people smoke cigarettes; 17.6 million are dependent on alcohol or abuse it. Marijuana still ranks as the No. 1 illegal drug. According to NIDA, 61.9 million people in the United States have experimented with marijuana.” The study group went on to note that the often-deadly “Black Tar” heroin had hit the streets of American cities the same summer. “Why was crack a big story [that summer] while Black Tar was not? One reason [is that] crack is depicted as moving into ‘our’—that is, the comfortable TV viewers’—neighborhood.”  

Fruit Fly Larvae Go Cold Turkey and Forget the Car Keys

Not a pretty sight.

Let’s start with the fruit fly, your basic Drosophila. A fruit fly, like a human, can become addicted to alcohol even at a very young age. The larval age. In other words, even as a maggot. And, just like humans, alcohol degrades a fruit fly maggot’s ability to learn. But adaption is an amazing thing, and drunken larvae eventually learn as well as their teetotaling cousins. That is, until the alcohol is taken away, in which case, the maggots become impaired learners once again. The larval nervous system goes haywire, and hyperexcitablity sets in. They can’t concentrate on their work. But one hour of “ethanol reinstatement” restores larval learning to normal levels.

It looks and sounds like withdrawal. Such effects in human alcoholics are often chalked up to state-dependent memory, but neurobiologists at the Waggoner Center for Alcohol and Addiction Research at the University of Texas, whose maggots these are, believe that state-dependent memory is not at work in the case of invertebrate ethanol dependence.

Brooks G. Robinson and associates fed the larvae a 5% ethanol supplement to their daily food. The maggots, incredibly enough, can reach blood-alcohol concentrations as high as 0.08, or roughly the legal limit for humans. If you blew a 0.08, the official chart says you would be suffering from impaired reasoning, disinhibition, and visual disturbances. For the maggots, no different. Larvae that fed on “ethanol food” for one hour learned poorly compared to straight maggots. The learning test, done before introducing alcohol into the picture, used a heat pulse to condition larvae away from an otherwise attractive odor. The reduced attraction to the odor is a form of associative learning.  Figuratively speaking, the drunken maggots kept burning themselves on the stove as they reached for the soup. They failed the field sobriety test.

But was it truly a case of impaired learning? Perhaps the drunken larvae had an impaired sense of smell. But the researchers could not document a reduced sense of odor based on responses with untrained animals. And both groups of maggots sensed heat equally, so the reduction in learning was not due to simple alcoholic anesthesia. Could the withdrawal response be due to the fact that alcohol is a calorie-rich food? To test that possibility, the researchers ran the experiment with sucrose instead of alcohol, and didn’t record any learning impairment in that case. As for state-dependent memory, the researchers assert in Current Biology that withdrawal effects “cannot be attributed to state-dependent learning, because the less than 20 minute training and testing assay for all treatment groups occurs on nonethanol plates.”

And finally, the investigators write, “the fact that both the withdrawal-induced learning deficit and the neuronal hyperexcitability responses are reversed by ethanol reinstatement suggests that they have related origins, and that withdrawal learning may suffer because the nervous system is overly excitable.”

So what have we learned? Well, alcohol dependence in humans is clearly associated with learning and memory deficits that can last for a year or more after quitting. Now that the researchers have demonstrated cognitive alcohol dependence in invertebrates—for the first time ever, they say—it may open the door to more sophisticated genetic analyses of alcoholism in Drosophila, for all the reasons that have drawn other biologists to the study of fruit flies over the years.

And there is more research to be done relative to the finding that neuronal hyper-excitability is linked in some way to the learning deficits caused by alcohol. A brief article by Stefan Pulver in the Journal of Experimental Biology  notes that the work of Robinson and colleagues “reinforces how eerily conserved ethanol’s physiological effects are across animal taxa. Alcohol addiction is truly the great leveller. It doesn’t matter whether you are man, mouse or maggot—over-consumption of alcohol will trigger very similar cellular and behavioral responses, with devastating consequences.” 

Robinson B., Khurana S., Kuperman A. & Atkinson N. (2012). Neural Adaptation Leads to Cognitive Ethanol Dependence, Current Biology, 22 (24) 2338-2341. DOI: 10.1016/j.cub.2012.10.038

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