We are sane, sober and responsible

poster-sane-sober

Bill White just posted on a cycle that entrenches stigma within some professions.

“There are whole professions whose members share an extremely pessimistic view of recovery because they repeatedly see only those who fail to recover.  The success stories are not visible in their daily professional lives.  We need to re-introduce ourselves to the police who arrested us, the attorneys who prosecuted and defended us, the judges who sentenced us, the probation officers who monitored us, the physicians and nurses who cared for us, the teachers and social workers who cared for the problems of our children, and the job supervisors who threatened to fire us.  We need to find a way to express our gratitude at their efforts to help us, no matter how ill-timed, ill-informed, and inept such interventions may have been.  We need to find a way to tell all of them that today, we are sane and sober and have taken responsibility for our own lives.  We need to tell them to be hopeful, that RECOVERY LIVES!  Americans see the devastating consequences of addiction every day; it is time they witnessed close up the regenerative power of recovery.”

 

 


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A new way to help addicted or alcoholic children

butterflies gaining strength and independenceThis is an encore post from My 3 Sunz

I’ve always supported recovery, but I thought that meant financing rehabs over and over – who can afford it? I used to wish that I could pay for the rehab-by-the-sea, thinking that would be the best-of-the-best for my son! Truth is, money can’t buy recovery and I’m grateful to have learned this before I continued to pour money down the drain not to mention, one more guilt feeling pushed aside. I have read a ton of books written by recovering addict/alcoholics and listened to others at open meetings. Each one led me to the same conclusion: recovery doesn’t cost money; it costs commitment, desire and willingness. Addiction costs money, and there is never enough.

So how do I help my son? By getting the tools to live life on life’s terms and not depend on him to make me happy. To learn how to accept him just the way he is and let him know he is loved. Recovery for him doesn’t have to cost me anything monetarily, it’s his for the taking yet I can still support him either way.

I discovered other ways to help – by indirectly supporting those who are ready for recovery. It may not be my son today, but it may be him tomorrow…There are nonprofits that help addicts looking for recovery and I can gift to them. When I struggle with birthdays and holidays as to what to gift my active addict alcoholic – I have to rethink how I do this. Today, I may write a check to a non-profit; I may support a local sober living environment or give my service to other entities that help educate the community. They are out there – the more I looked, the more I found them. Helping this way gives me a sense of gratitude – it’s my new way of helping my loved ones.

The Social Brain: Weekend Reading Links II

This month I have focussed on social neuroscience topics relevant to cognition and social function. 

Here are a few interesting abstracts culled from over 200 that I have reviewed from PubMed.

Abstract links will have links to free full-text articles.

I will be picking a few from this list for more discussion in posts for the remainder of September.

Social Learning in Humans

This review examines the existing research on social learning in both humans and other animals. Social learning appears key in many animal species. Humans appear to have some common and distinct features of social learning.

Social Cognition and Social Decision Making

Cognition commonly leads to making decisions and carrying out a behavior. However, the link between cognition and decision-making in the social domain is poorly understood. These links have implications in the economic decision making domain.

Social Cognition and the Brain Default Mode Network

Functional MRI provides a tool to understand the brain default connectivity network in humans. The medial prefrontal medial cortex (mPFC) is known to be involved in key social cognition. This review examines how default mode connections between the mPFC and other regions can provide insight into social cognition. 

Social Brain Structure in Autism and Schizophrenia

Both autism and schizophrenia are brain disorders known to include impairment in social cognition. In this study, brain structural abnormalities are compared between those with autism and schizophrenia. The study finds important differences in brain insula regions. 

Gift Giving: Women Do It Better

Women appear to have several advantages over men in social cognition and social decision making. In this study, women and men are compared in their ability to select gifts and women consistently select better gifts than men. The correlates of this social decision making process is examined.

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FAST Generics Act Would Amend the FDC Act to Address REMS/Restricted Access Programs and Biostudy Sample Availability

By Kurt R. Karst –      

There have been rumors floating around Washington, DC for a few months that efforts were afoot to introduce legislation to amend the FDC Act to address the availability of products subject to a restricted distribution program to generic drug and biosimilar manufacturers for purposes of conducting studies necessary to pursue approval of a marketing application.  Those rumors turned into reality with the September 18th introduction of H.R. 5657, the Fair Access for Safe and Timely Generics Act of 2014 (“FAST Generics Act”).  Introduced in the U.S. House of Representatives by Congressmen Steve Stivers (R-OH) and Peter Welch (D-VT), the bill would “increase consumer access to generic drugs, boost market competition and ultimately save consumers money,” according to a press release announcing the introduction of the FAST Generics Act.  The Generic Pharmaceutical Association, which sponsored a paper published in July 2014 on restricted distribution programs and generic drug competition, applauded the introduction of the bill in a press release.

In case you’re not familiar with the topic of the FAST Generics Act, the issue concerns drug and biological products covered by restricted distribution programs – either under a Risk Evaluation and Mitigation Strategies (“REMS”) program with Elements To Assure Safe Use (“ETASU”) under FDC Act § 505-1, or under a restricted distribution program adopted and implemented by a brand-name manufacturer.  In most cases, in order for a generic drug (or biosimilar) manufacturer to submit a marketing application to FDA, the company must first conduct studies comparing its proposed product to the brand-name reference product.  In order to do so, the generic drug manufacturer must first obtain reference product sample.  Normally drug product sample is easily obtained through various market channels.  Products under a restricted distribution program, however, are tightly controlled (often because of a safety concern) and are not readily available.  If a generic drug sponsor is unable to obtain sample for equivalence testing, then it is unable to seek marketing approval from FDA.

Current law states that “[n]o holder of an approved covered application shall use any element to assure safe use required by [FDA] under [FDC Act § 505-1(f)] to block or delay approval of an application under section 505(b)(2) or (j) or to prevent application of such element under [FDC Act § 505-1(i)(1)(B)] to a drug that is the subject of an [ANDA].”  In June 2009, Dr. Reddy’s Laboratories, Inc. submitted a Citizen Petition (Docket No. FDA-2009-P-0266) to FDA requesting that the Agency “establish procedures to facilitate the availability of generic versions of drug products subject to a [REMS] and enforce the FDC Act to prevent companies from using REMS to block or delay generic competition.”  FDA responded to the petition in August 2013 saying, among other things, that decisions to take enforcement action are made at the Agency’s discretion on a case-by-case basis and that FDA “agrees that issues related to ensuring that marketplace actions are fair and do not block market competition would be best addressed by the FTC,” to which FDA has been referring complaints related to restricted distribution programs. 

In 2012, as Congress was considering legislation that was ultimately enacted as the FDA Safety and Innovation Act (“FDASIA”), there was a push to amend the law to address REMS and generic competition.  Specifically Section 1131 of Senate-passed S. 3187 would have amended FDC Act § 505-1 to state that:

Notwithstanding any other provision of law, if a drug is a covered drug, no elements to ensure safe use shall prohibit, or be construed or applied to prohibit, supply of such drug to any eligible drug developer for the purpose of conducting testing necessary to support an application under [FDC Act § (b)(2) or § 505(j) or PHS Act § 351(k)] if the Secretary has issued a written notice described in paragraph (2), and the eligible drug developer has agreed to comply with the terms of the notice.

That provision was not enacted as part of FDASIA.  As one legislative bulletin issued at the time stated, “[s]ome controversy surrounded this provision since it could have [led] to the FDA forcing drug sales between brand and generic manufacturers.”  In addition, then-FTC Commissioner J. Thomas Rosch objected to including the provision in FDASIA.  Referring to both REMS legislation advocated by FTC staff that would “give the FTC jurisdiction to challenge the refusal of a pioneer drug company to provide product samples to generic manufacturers if the FDA determined that the generic company’s protocols were safe,” and to the REMS provisions in S. 3187, Commissioner Rosch commented that “[n]either proposal should be tacked on to other legislation on the Senate floor and should instead be considered by the Help Committee on their own merits” (see our previous post here). 

Meanwhile, issues concerning ETASU REMS, restricted distribution programs, and generic competition were being debated in court in the context of antitrust law (see our previous posts here, here, and here).  None of the earlier court challenges resulted in a decision, because the cases were settled.  Earlier this year, however, Mylan Pharmaceuticals Inc. filed a lawsuit alleging that Celgene Corporation violated federal and state antitrust laws by preventing generic competition for Celgene’s drug products THALOMID (thalidomide) Capsules and REVLIMID (lenalidomide) Capsules (see our previous post here).  That case is still pending, with a Motion to Dismiss filed by Celgene (Opposition and Reply briefs are available here and here).

The 17-page FAST Generics Act would amend the FDC Act to add Section 505-2, titled “Competitive Access to Covered Products for Development Purposes.”  Proposed FDC Act § 505-2 would add several provisions, including:

(b) COMPETITIVE ACCESS TO COVERED PRODUCTS AS A CONDITION ON APPROVAL OR LICENSING.—As a condition of approval or licensure, or continuation or renewal of approval or licensure, of a covered product under section 505 of this Act or section 351 of the Public Health Service Act, respectively, the Secretary shall require that the covered product’s license holder not adopt, impose, or enforce any condition relating to the sale, resale, or distribution of the covered product, including any condition adopted, imposed, or enforced as an aspect of a risk evaluation and mitigation strategy approved by the Secretary, that restricts or has the effect of restricting the supply of such covered product to an eligible product developer for development or testing purposes. 

(c) COMPETITIVE ACCESS TO COVERED PRODUCTS OTHER THAN REMS PRODUCTS FOR DEVELOPMENT PURPOSES.—No license holder shall adopt, impose, or enforce any condition relating to the sale, resale, or distribution of a covered product that interferes with or restricts access to reasonable quantities of a covered product by an eligible product developer for development and testing purposes, at commercially reasonable, market-based prices, from the license holder or from any wholesaler or specialty distributor authorized by the license holder to commercially distribute or sell the covered product unless the license holder generally adopts, imposes, or enforces lawful conditions relating to the sale, resale, or distribution of a covered product, with respect to other buyers of the covered product.

(d) COMPETITIVE ACCESS TO REMS PRODUCTSFOR DEVELOPMENT PURPOSES.—

(1) PROHIBITED USE OF REMS TO RESTRICTACCESS.—With respect to a REMS product, no aspect of a risk evaluation and mitigation strategy under section 505–1 shall prohibit or restrict, or be construed or applied to prohibit or restrict, the supply of such REMS product to an eligible product developer for development and testing purposes, at commercially reasonable, market-based prices, from the REMS product’s license holder or from any wholesaler or specialty distributor authorized by the license holder to commercially distribute or sell the REMS product.

(2) SINGLE, SHARED SYSTEM OF ELEMENTS TO ASSURE SAFE USE.—With respect to a REMS product, no license holder shall take any step that impedes—

(A) the prompt development of a single, shared system of elements to assure safe use under section 505–1; or

(B) the entry on commercially reasonable terms of an eligible product developer into a previously approved system of elements to assure safe use.

(e) PROCEDURES FOR OBTAINING ACCESS TO COVERED PRODUCTS.—

(1) COMPETITIVE ACCESS.—Notwithstanding any other provision of law, in the case of an eligible product developer that has an authorization to obtain a covered product in effect . . . , no license holder shall adopt, impose, or enforce any other condition relating to the sale, resale, or distribution of such covered product that interferes with or restricts access to reasonable quantities of the covered product by the eligible product developer for development and testing purposes, at commercially reasonable, market-based prices, from the license holder or from any wholesaler or specialty distributor authorized by the license holder to commercially distribute or sell the covered product, unless the license holder generally adopts, imposes, or enforces lawful conditions relating to the sale, resale, or distribution of a covered product, with respect to other buyers of the covered product.

A violation of a requirement or prohibition in any of the above-proposed sections would be treated, in the case of a REMS product, as a violation of the product’s REMS, and would be a prohibited act under proposed FDC Act § 301(ddd).  Also, an “eligible product developer” (i.e., a person seeking to develop an ANDA, 505(b)(2) application, or a BLA) that has authorization for access to a covered product from FDA and that is aggrieved by a violation of one of the above-proposed sections “by a license holder or any wholesaler or specialty distributor authorized by the license holder to commercially distribute or sell the covered product[,] may sue such license holder for injunctive relief and treble damages (including costs and interest of the kind described in section 4(a) of the Clayton Act (15 U.S.C. 15(a)).”

In addition to laying out the procedures for an interested party to obtain an authorization to procure a covered product, the FAST Generics Act would give FDA the authority to prohibit, limit, or otherwise suspend a transfer of a covered product to an eligible product developer because such transfer would present an imminent hazard to the public health, and would shield NDA and BLA holders from liability for any claim arising out of an eligible product developer’s development or testing activities conducted under proposed FDC Act § 505-2, “including a claim arising out of a failure of the eligible drug developer to follow adequate safeguards to assure safe use of the covered product.”

Finally, the bill would require various reports from FDA and from the FTC on the implementation of proposed FDC Act § 505-2, and would amend FDC Act § 505-1(i)(1)(B) concerning waiver of the single, shared REMS requirement (see our previous post here).  If enacted, the bill would apply to all NDAs and BLAs, regardless of whether or not those applications were approved before, on, or after the date of enactment of the FAST Generics Act. 

“Tracking the Trends: Insights from the Drug Testing Index” Webinar

Tracking the Trends webinarThe Quest Diagnostics Drug Testing Index™ (DTI) is arguably the industry’s longest standing, most frequently relied upon resource for drug use patterns within the American workforce. Our presenter, Dr. Barry Sample, Director of Science and Technology, Quest Diagnostics, is responsible gathering, publishing and interpreting the trends found within the data.

Join us on Tuesday, October 7 at 1 p.m. CT for a webinar, “Tracking the Trends: Insights from the Drug Testing Index,” that will highlight key findings and the latest drug test positivity data by workforce type, testing reason, drug category and specimen type. Register now.

Genetics of Social Skills: Oxytocin Receptor Gene

Social neuroscience is an emerging emphasis in the field of neuroscience research.

Social cognition is the subset of cognitive functions related to social processes and includes factors such as facial recognition, social memory and ability to form friendships and other social bonds.

Impairment in social cognition is a known feature in autism, schizophrenia and other mental disorders. This type of impairment can produce significant problems in life adjustment, employment and human attachment.

Genetic features appear to be important in human social cognition. Biological factors influence social behavior including the action of the hormone oxytocin.

Dave Skuse along with colleagues in England, Finland and the U.S. recently published an important study examining the oxytocin receptor gene and social cognition.

Their study used a family study design of 198 families from the U.K. and Finland with a single identified with high-functioning autism.

This strategy was used with recognition that social cognition deficits are common in family members of those with autism and autism spectrum disorder.

Probands with autism and family members had genetic testing for oxytocin gene polymorphism status along with the related vasopression gene

All participants completed a standardized test known as the Facial Recognition Memory Test (FRMT). Facial recognition and memory are key elements in social cognition and social function.

The key findings from the study included the following:

  • Oxytocin receptor polymorphism SNP rs237887 was strongly linked to deficits in facial recognition memory
  • Homozygous status for this SNP was associated with approximately a one standard deviation reduction in performance on the FRMT.
  • This deficit was found in the autism group along with a significant number of undiagnosed family members

The authors note their finding is consistent with other studies linking this specific SNP polymorphism with measures of empathy, autism traits and emotional responsivity to betrayal cues

The authors also note their results add to rodent animal model studies finding a key role for the oxytocin and vasopressin system in modulating social cognition and social behavior.

These types of studies hold promise for potential drug development to reduce social impairment in those with autism and other disorders of social cognition.

Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link in the citation below.

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Skuse DH, Lori A, Cubells JF, Lee I, Conneely KN, Puura K, Lehtimäki T, Binder EB, & Young LJ (2014). Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. Proceedings of the National Academy of Sciences of the United States of America, 111 (5), 1987-92 PMID: 24367110

Wanting the Pain to Stop from the worry of addiction

1179314_28920035 angry boySometimes the pain of watching our loved one implode due to their addiction seems more than we can bear. I remember when my daughter was in the throes of her addiction how I was in so much pain that I just wanted to dig a hole and crawl in. I daydreamed about just getting in my car and driving, not in any particular direction but just putting distance between me and the situation that caused so much pain. I talk to many parents who have kids who have gone from recreational experimentation to destructive addiction and one common denominator is the heart wrenching pain that we experience. It’s like a slow motion train wreck, you see it happening and yet it seems there is nothing you do to stop it.
Even though we can’t seem to stop the oncoming train, we can focus on how we can take care of ourselves and begin to breathe again, and get our life back together. We can look at what we are grateful for and focus on other loved ones that many times don’t get the attention they deserve because the one with addiction is all consuming. We can look at how to better take care of ourselves whether it’s exercise or sleep or spending time with friends. The good news is that by taking care of ourselves it can sometimes have a positive effect on the one who is afflicted with addiction. It reminds me of a prayer that became a mantra for me, ‘God, Change nothing in my life, change me’. When we change ourselves, the world around benefits.

“Thou Shalt Not”: FDA Issues Two Guidances on ANDA Refuse-to-Receive Issues on the Eve of GDUFA Public Meeting

By Kurt R. Karst –      

There are mortal sins and there are venial sins.  In the latest guidance documents FDA announced (here and here) earlier this week – a final guidance on ANDA Refuse-to-Receive (“RTR”) standards and a draft guidance on ANDA RTR for lack of proper justification of impurity limits – FDA focuses on the mortal sins of ANDA submission that will generally result in the Office of Generic Drugs (“OGD”) refusing to accept an ANDA for review.  Indeed, the phrase “FDA will refuse-to-receive an ANDA” (followed by or preceded by some example) appears not less than 24 times in FDA’s final ANDA RTR standards guidance. 

Both ANDA RTR guidances were issued on the eve of a September 17th public meeting on implementation of the Generic Drug User Fee Amendments of 2012 (“GDUFA”).  FDA requested comment at the meeting on the ANDA RTR impurity limits draft guidance and other recent guidances on GDUFA implementation (see our previous posts here, here, and here).  FDA also solicited comment on “GDUFA Implementation Related to Generic Drug Exclusivity” and “GDUFA Implementation and Potential First Generics.”  Although very few comments (see here) were submitted to FDA in response to the Agency’s solitation, we understand that the public meeting was well attended and included statements from an array of generic drug industry stakeholders, including the Generic Pharmaceutical Association (see here and here).  The September 17th public meeting follows a solitication from FDA earlier this year seeking input and suggestions on ways to improve the quality of ANDAs and on how to best communicate those suggestions to the generic drug industry (see our previous post here).  About a dozen comments have been submitted to the docket FDA established for that solicitation.

FDA’s ANDA RTR standards guidance finalizes a draft version of the guidance released in October 2013.  In addition to providing greater clarity around major deficiencies (i.e., mortal sins) that will generally result in an RTR decision and minor deficiencies (i.e., venial sins) that can be easily corrected, the guidance makes several important changes to the draft version.  Bob Pollock from Lachman Consultants covers those changes in his recent post

In the ANDA RTR impurity limits draft guidance – a guidance FDA presumably issued in draft form and separate from the ANDA RTR standards guidance because the issue was not addressed in the draft ANDA RTR standards guidance – FDA lays out serious deficiencies in impurity information that could cause FDA to RTR an ANDA. The deficiencies described in the draft guidance include: “(1) Failing to justify proposed limits for specified identified impurities in drug substances and drug products that are above qualification thresholds; (2) failing to justify proposed limits for specified unidentified impurities that are above identification thresholds; and (3) proposing limits for unspecified impurities (e.g., any unknown impurity) above identification thresholds.” 

As Bob Pollock notes, the position FDA takes in the draft guidance “is consistent with past Guidance issued by OGD on the requirements for justification of impurity limits, but, in the past, OGD has not stated that if such justification is lacking, they will issue an RTR letter rather than handling the issue as a review issue.”  This is an important observation, because it shows that OGD is making an effort to clarify the sometimes fuzzy line between what constitutes a deficiency for ANDA RTR purposes, and what is properly an ANDA review issue (and not an RTR issue).  Indeed, we’re likely to see more follow-on, issue-specific guidances like the ANDA RTR impurity limits draft guidance as the new ANDA filing and review groups within OGD hash things out and establish brighter lines between ANDA filing and review issues.  FDA says as much in the notice announcing the ANDA RTR impurity limits draft guidance: “FDA intends to develop additional guidance documents further clarifying the enhanced refusal to receive standards.”

Why Will Power Fails


How to strengthen your self-control.

(First published August 12, 2013)

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.


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