Posts Tagged ‘dopamine’

Suggestible You 10

March 26, 2017

“Suggestible You” is the title of a book by Erik Vance.  The subtitle is “The Curious Science of Your Brain’s Ability to Deceive, Transform, and Heal.     This is the tenth post on this book.  This post describe the role of  placebos in addiction.

Approximately 1 in 10 Americans is addicted to some kind of drug—mostly alcohol, although opioid addiction is gaining quickly.  Traditionally addiction has been viewed as a moral failing or a lack of willpower.  Today we understand addiction is mostly physiological, specifically around dopamine.  This is not surprising since this neurotransmitter deals with the anticipation and enjoyment of rewards.  Vance note that this includes sugar, sex, money, a high score on Grand Theft, as well as drugs.

Unfortunately, drug use doesn’t just change the way you feel for a couple of hours: it can also change the brain itself.  When the nervous system is presented with an abundance of pleasurable chemical stimulation through drug use, the nervous system gets overwhelmed and shuts down its production of dopamine to bring itself back into equilibrium.  This creates a bad feedback loop in which the person finds himself short on dopamine whenever he’s not using the drug.   Food no longer tastes as good, and sex can lose its thrill.  Taking the drug that caused this problem is the only way to get back to something close to normal.

Addiction literally changes the way the brain works.  Not only do addicts have less dopamine from drug overuse, but also their  dopamine receptors are affected (either changing their numbers or changing how well they transmit messages).  Regular drug uses twists memories so both the drug and the circumstances surrounding the drug use.  Addiction causes the brain’s impulse control centers to shut down, which greatly increases the chances of relapse.  If cocaine addicts are shown an image of blow for as little as 33 milliseconds, which is too fast to register in consciousness, they will have immediate cravings.

Vance sees addiction as sort of a perversion of all the brain circuits and processes  in his book.  Consequently he thinks that suggestion and expectation may hold the answers to overcoming it.  Naloxone, the drug that first helped expose the chemical nature of placebos and blocks placebo responses altogether, wasn’t invented for placebo research.  It serves a crucial role in medicine as an emergency treatment for drug overdoses.  It’s also pretty effective at blocking the effects of heroin or oxycodone.
A closely related drug, naltrexone, is one of the most effective treatments for alcohol abuse.

People get tipsy when a nonalcoholic beer is substituted for an alcoholic beer.  This also works the other way.  A study at Minot State University doctored root beer to give it the same alcohol level as regular beer.The researchers offered the doctored drink to a group of unsuspecting volunteers, while another group received regular beer.  Not surprisingly, both groups got tipsy after a few drinks. What is interesting is that those who drank beer actually absorbed more alcohol into their blood than those who thought they were drinking soda but were in fact consuming just as much alcohol.

It is clear that work on treatment is still a work in progress, but progress is being made.

Some two million Americans are addicted to prescription opioid drugs and about 19,000 died from overdoses in 2014.  This is about twice the number who died from heroin overdoses, and three times the number who died from cocaine.  One theory of pain is that after an injury, the pain never leaves, it just gets gradually covered up by the body’s internal medicine.  A team led by Bradley Taylor gave naloxone to patients who had recovered from an injury and for many of them the pain came right back as if pain had been hiding under the surface for this whole time.  These patients displayed some of the hallmarks of opioid withdrawal.  During the process of recovering from pain, we actually become dependent on our own opioids.   Taylor thinks that this may be the key to understanding not only addiction, but also the switch from short-term to chronic pain.

Given this understanding, NIH researcher Luana Colloca, whom we have encountered previously, is studying the role placebos my play.  She mixed a few placebo pills into a group of pain patients’ medication.  Each week they have five or six pain pills and one or two placebos.  As the week progressed, she upped the placebos and topped the opioids until the artificial was administered only about half the time.  The results of the project are not reported, but the idea is clear.  The patient is trained to expect pain relief when taking a pill.  Gradually she takes the pill away and lets the patient’s own expectation cover the pain relief.  The patient uses her expectations to switch from an external drug to an internal one.

“Suggestible You” is the title of a book by Erik Vance.  The subtitle is “The Curious Science of Your Brain’s Ability to Deceive, Transform, and Heal.     This is the tenth post on this book.  This post describe the role of  placebos in addiction.

Approximately 1 in 10 Americans is addicted to some kind of drug—mostly alcohol, although opioid addiction is gaining quickly.  Traditionally addiction has been viewed as a moral failing or a lack of willpower.  Today we understand addiction is mostly physiological, specifically around dopamine.  This is not surprising since this neurotransmitter deals with the anticipation and enjoyment of rewards.  Vance note that this includes sugar, sex, money, a high score on Grand Theft, as well as drugs.

Unfortunately, drug use doesn’t just change the way you feel for a couple of hours: it can also change the brain itself.  When the nervous system is presented with an abundance of pleasurable chemical stimulation through drug use, the nervous system gets overwhelmed and shuts down its production of dopamine to bring itself back into equilibrium.  This creates a bad feedback loop in which the person finds himself short on dopamine whenever he’s not using the drug.   Food no longer tastes as good, and sex can lose its thrill.  Taking the drug that caused this problem is the only way to get back to something close to normal.

Addiction literally changes the way the brain works.  Not only do addicts have less dopamine from drug overuse, but also their  dopamine receptors are affected (either changing their numbers or changing how well they transmit messages).  Regular drug uses twists memories so both the drug and the circumstances surrounding the drug use.  Addiction causes the brain’s impulse control centers to shut down, which greatly increases the chances of relapse.  If cocaine addicts are shown an image of blow for as little as 33 milliseconds, which is too fast to register in consciousness, they will have immediate cravings.

Vance sees addiction as sort of a perversion of all the brain circuits and processes  in his book.  Consequently he thinks that suggestion and expectation may hold the answers to overcoming it.  Naloxone, the drug that first helped expose the chemical nature of placebos and blocks placebo responses altogether, wasn’t invented for placebo research.  It serves a crucial role in medicine as an emergency treatment for drug overdoses.  It’s also pretty effective at blocking the effects of heroin or oxycodone.
A closely related drug, naltrexone, is one of the most effective treatments for alcohol abuse.

People get tipsy when a nonalcoholic beer is substituted for an alcoholic beer.  This also works the other way.  A study at Minot State University doctored root beer to give it the same alcohol level as regular beer.The researchers offered the doctored drink to a group of unsuspecting volunteers, while another group received regular beer.  Not surprisingly, both groups got tipsy after a few drinks. What is interesting is that those who drank beer actually absorbed more alcohol into their blood than those who thought they were drinking soda but were in fact consuming just as much alcohol.

It is clear that work on treatment is still a work in progress, but progress is being made.

Some two million Americans are addicted to prescription opioid drugs and about 19,000 died from overdoses in 2014.  This is about twice the number who died from heroin overdoses, and three times the number who died from cocaine.  One theory of pain is that after an injury, the pain never leaves, it just gets gradually covered up by the body’s internal medicine.  A team led by Bradley Taylor gave naloxone to patients who had recovered from an injury and for many of them the pain came right back as if pain had been hiding under the surface for this whole time.  These patients displayed some of the hallmarks of opioid withdrawal.  During the process of recovering from pain, we actually become dependent on our own opioids.   Taylor thinks that this may be the key to understanding not only addiction, but also the switch from short-term to chronic pain.

Given this understanding, NIH researcher Luana Colloca, whom we have encountered previously, is studying the role placebos my play.  She mixed a few placebo pills into a group of pain patients’ medication.  Each week they have five or six pain pills and one or two placebos.  As the week progressed, she upped the placebos and topped the opioids until the artificial was administered only about half the time.  The results of the project are not reported, but the idea is clear.  The patient is trained to expect pain relief when taking a pill.  Gradually she takes the pill away and lets the patient’s own expectation cover the pain relief.  The patient uses her expectations to switch from an external drug to an internal one.

Suggestible You 5

March 21, 2017

“Suggestible You” is the title of a book by Erik Vance.  The subtitle is “The Curious Science of Your Brain’s Ability to Deceive, Transform, and Heal.  This book is about the placebo response and related phenomena.   This is the fifth post on this book.

Vance describes the story of a man diagnosed ten years ago being severely debilitated in late stage Parkinson.  He volunteered for an experiment in which the medication was directly injected into a critical part of the brain.  To control for the placebo effect, these experiments require sham surgery that copies everything about the surgery except for the critical drug injected into the brain.  The study involved 51 participants.  Twenty-four people got the real surgery and 27 got the sham surgery.  The drug proved to be a failure.  However, the participant of interest did show a remarkable recovery.  However, he was one of those who had received sham surgery.

This dramatic example makes the point that there are large individual differences in the response to placebos.  Kathryn Hall of Harvard University was interested in studying possible genetic bases for this enhanced responsively.  She discovered the COMT gene.  The COMT genes codes for an enzyme in the brain, also called COMT, or catechol-O-methyltransferase.  Vance writes that this is one of the best-studied brain pathways in the world, and may be the most fascinating link he has discovered as a science writer.

Here’s how it works.  Dopamine has enormous power and is important for body movement and good moods.  However, it is possible to have too much of a good thing.  A mechanism is need to sweep up the bits we don’t need—the extra dopamine molecules floating around our skull that aren’t doing anything useful.  COMT gets rid of the excess dopamine molecules.  COMT is an extremely long and complicated enzyyme.  Fortunately, it is one within its machinery that defines how well it works.  Depending upon an individual’s genetics there are two types of this crucial portion of the enzyme:  valine (val) or methionine (met).  If one’s brain has val in that one spot, the enzyme performs its job of removing excess dopamine.  However, if the enzyme has met in that one spot, it is much less effective.  The brain is left with lots of excessive dopamine.

Remember that each trait in the body is a combination from each of the parents.  COMT works in a similar manner.  So we have val/met, but also val/vals and met/mets.  So 25% of the population are val/vals,and 25% are met/mets, 50% of the population are val/mets.

Hall conducted an experiment pairing COMT genes with placebos.  She enrolled 262 patients with irritable bowel syndrome (IBS) into an experimental treatment involving acupuncture.  She selected patients with either moderate or severe cases of IBS and then divided them into three groups. One group, the true control group, was put on a waiting list and given nothing.  The other two groups were told that they would get acupuncture, but they were unknowingly given fake acupuncture.  Half of the participants got treatment from a comforting, caring acupuncturist while the others got treatment from a cold, uncaring acupuncturist.

Here are the results.  People on the waiting list stayed the same regardless of their genes.

Met/mets with the uncaring acupuncturist  did better than the val/vals, but just barely.

Val/vals with the caring acupuncturist did about as well as the val/vals with the uncaring acupuncturist and all the people on the waiting list. In short, no placebo effect.

The val/mets who got the caring acupuncturist did about five times better.

The results of the met/mets who got the caring doctor went through the roof.

Clearly the kind words  meant something totally different to one genotype than it did with the others.  Hall had divided the placebo responders into measurable groups.Met/mets—those people who were born with lazy enzymes and a little too much dopamine in their responses were more prone to placebo responses.

Although the COMT gene plays a large role in the creation of the COMT enzyme, it’s not the only gene that does so.  Other genes help build the enzyme that can boost or cripple its performance, as well as all the other genes in you body that affect dopamine.    COMT also goes after epinephrine and norepinephrine, neurotransmitters that are key to regulating adrenaline, cardiac, function, and our response to stress.

So, in summary, the interactions are complex.  But different factors that contribute to the immune response are being identified.  Genes, the administrator of the placebo, and our fellow human beings are factors.

Denying the Grave: Why We Ignore the Facts that Will Save Us

March 13, 2017

“Denying the Grave:  Why We Ignore the Facts that Will Save Us” is the third of three books of three books to be reviewed from an article titled, “That’s What You Think:  Why reason and evidence won’t change our minds” by Elizabeth Kolbert in the 27 February 2017 issue of “The New Yorker.”

The authors of this book are a psychiatrist, Jack Gorman, and his daughter, Sara Gorman, a public health specialist.  They probe the gap between what science tells us and what we tell ourselves.  Their concern is with those persistent beliefs which are not just demonstrably false, but also potentially deadly, like the conviction that vaccines are hazardous.

The Gormans argue that ways of thinking that now seem self-destructive must at some point have been adaptive.  They dedicate many pages to the confirmation bias, which they claim has a physiological component.  This research suggests that people experience genuine pleasure—a rush of dopamine—when processing information that supports their beliefs.  They observe,”It feels good to ‘stick to our guns’ even if we are wrong.”

The Gormans do not just want to catalogue the ways we go wrong;  they want to correct them.  Providing people with accurate information does not seem to help; people simply discount it.  They write that “the challenge that remains is to figure out how to address the tendencies that lead to false scientific belief.”

Designed to Addict

September 8, 2016

Designed to Addict is the title of the second chapter in “The Cyber Effect” by Dr. Mary Aiken.  Although the internet was not designed to addict users, it appears that it is addicting many.  Of course, humans are not passive victims, they are allowing themselves to be addicted.  Dr. Aiken begins with the story of a twenty-two year old mother Alexandra Tobias.  She called 911 to report that her three-month old son had stopped breathing and needed to be resuscitated.  She fabricated a story to make it sound as if an accident had happened, but later confessed that she was playing “Farmville” on her computer and had lost her temper when her baby’s crying distracted her from the Facebook game.  She picked up the baby and shook him violently and his head hit the computer.  He was pronounced dead at the hospital dead from head injuries and a broken leg.

At the time of the incident “Farmville” had 60 million active users and was described by its users in glowing terms as being highly addictive.  It was indeed addictive so that “Farmville” Addicts Anonymous support groups were formed and a FAA page was created on Facebook.    Dr. Aiken found this case interesting as a forensic cyberpsychologist for the following reason:  the role of technology in the escalation of an explosive act of violence.  She described it as extreme impulsivity, an unplanned spontaneous act.

Impulsivity is defined as “a personality trait characterized by the urge to act spontaneously without reflecting on an action and its consequences.”  Dr. Aiken notes “that the trait of impulsiveness influences several important psychological processes and behaviors, including self-regulation, risk-taking and decision making.  It has been found to be a significant component of several clinical conditions, including attention deficit/hyperactivity disorder, borderline personality disorder, and the manic phase of bipolar disorder, as well as alcohol and drug abuse and pathological gambling.”  Dr. Aiken takes care to make the distinction between impulsive and compulsive.  Impulsive behavior is a rash, unplanned act, whereas compulsive behavior is planned repetitive behavior, like obsessive hand washing.  She elaborates in cyber terms.  “When you constantly pick up your mobile phone to check your Twitter feed, that’s compulsive.  Then  you read a nasty tweet and can’t restrain yourself from responding with an equally  nasty retort (or an even nastier one), that’s impulsive.”

Joining an online community or playing in a multiplier online game can give you a sense of belonging.  Getting “likes” meets a need for esteem.  According to psychiatrist Dr. Eva Ritvo in her article “Facebook and Your Brain” social networking “stimulates release of loads of dopamine as well as offering an effective cure to loneliness.  These “feel good” chemicals are also triggered by novelty.  Posting information about yourself can also deliver pleasure.  “About 40 percent of daily speech is normally taken up with self-disclosure—telling others how we feel or what we think about something—but when we go online the amount of self-disclosure doubles.   According to Harvard neuroscientist Diana Tamir, this produces a brain respond similar to the release of dopamine.”

Jack Panksepp is a Washington State University Neuroscientist who coined the term affective neuroscience, or the biology of arousing feelings or emotions.  He argues that a number of instincts such as seeking, play, anger, lust, panic, grief, and fear are embedded in ancient regions of the human brain built into the nervous system as a fundamental level.  Panskepp explains addiction as an excessive form of seeking.  “Whether the addict is seeking a hit from cocaine, alcohol, or a Google search, dopamine is firing, keeping the human being in a constant state of alert expectation.”

Addiction can be worsened by the stimuli on digital devices that come with each new email or text to Facebook “like,” so keep them turned off unless there is a good justification for keeping them on, and then only for a designated amount of time.

There is technology to help control addictive behavior.  One of these is Breakfree, an app that monitors  the number of times you pick up your phone, check your email, and search the web.  It offers nonintrusive  notifications and provides you with an “addiction score” every day, eery week, and every month to track your progress.  There are many more such apps such as Checky and Calm, but ultimately it is you who needs to control your addictions.

Mindfulness is a prevalent theme in the healthy memory blog.  It is a Buddhist term “to describe the state of mind in which our attention is directed to the here and now, to what is happening in the moment before us, a way of being kind to ourselves and validating our own experience.”    As a way of staying mindful and keeping track of time online, Dr. Aiken has set her laptop computer to call out the time, every hour on the hour, so that even as she is working in cyberspace, where time flies, she is reminded very hour of the temporal real world.”

Internet addictive behavior expert Kimberly Young recommends three strategies:
1.  Check your checking.  Stop checking your device constantly.
2.  Set time limits.  Control your online behavior—and remember , kids will model
their behavior on adults.
3.  Disconnect to reconnect.  Turn off devices at mealtimes—and reconnect with                  the family.
Some people find what are called internet sabbaths helpful and disconnect for a day or a weekend.  Personally HM believes in having a daily disciplined schedule to prevent a beneficial activity from becoming a maladaptive behavior.

Much more is covered in the chapter, to include compulsive shopping, but the same rule applies.  To be aware of potential addiction monitor your behavior, and make the appropriate modifications.

© Douglas Griffith and healthymemory.wordpress.com, 2016. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Douglas Griffith and healthymemory.wordpress.com with appropriate and specific direction to the original content.

You Have Two Brains

December 26, 2012

As do I. It was described by Byron Robinson in The Abdominal and Pelvic Brain in 1907 and named the enteric nervous system (ENS) by Johannis Langley.1 About the same time it was found that the ENS can act autonomously. When its main connection with the brain, the vagus nerve, is severed the ENS still is capable of coordinating digestion. Interest in this gut brain dropped until the field of neurogastroenterology was born in the 1990’s. It has since been learned that about 90% of the signals passing along the vagus nerve come not from the brain above, but from the ENS.2

How do these two brains compare? Both have barriers restricting blood flows to their respective brains and are supported by glial cells. The first brain consists of about 85 billion neurons; the second brain has about 500,000 neurons. 100 neurotransmitters have been identified for the first brain; 40 neurotransmitters have been identified for the second brain. Each brain produces about half of the body’s dopamine. The first brain produces 5% of all serotonin. The second brain produces 95% of all serotonin. This final comparison is quite telling. Serotonin is best known as the “feel-good” molecule. It is involved in preventing depression and in regulating sleep, appetite, and body temperature. Serotonin produced in the gut gets into the bloodstream, where it plays a role in repairing damaged cells in the liver and lungs. Moreover, it is important for the normal development of the heart, as well as in the regulation of bone density by inhibiting bone formation.

Serotonin produced in the ENS affects mood by stimulating the vagus nerve. Research has shown that stimulation of the vagus nerve can be an effective treatment for chronic depression that has failed to respond to other treatments.3 These gut to brain signals via the vagus nerve might also explain why fatty foods make us feel good. Brain scans of volunteers given a dose of fatty acids directly into the gut had a lower response to pictures and music designed to make them feel sad that a control group given saline. The fatty acid group also reported being only about half as sad as the control group.4

Stress leads the gut to increase its production of ghrelin. Ghrehlin is a hormone that makes you feel hungrier as well as reducing anxiety and depression. It stimulates the release of dopamine in the brain both directly, by directly triggering pleasure and reward pathways, and indirectly by signals triggered via the vagus nerve. At one time during our evolutionary past, the stress-busting effect of ghrelin might have been useful, but today the result of chronic stress or depression can be chronically elevated ghrelin leading to obesity.

The second brain has also been implicated in a variety of first brain disorders. In Parkinson’s disease the problems with movement and muscle control are caused not only by loss of dopamine producing cells in the first brain, but also by dopamine producing cells in the second brain due to Lewy bodies. It is even suspected that the disease starts in the second brain as the result of some trigger such as a virus, and then spreads to the brain via the vagus nerve. Similarly the characteristic plaques and tangles found in the first brains of people with Alzheimer’s are present in their second brains also.

Cells in the second brain could be used as the basis for treatments. One experimental intervention for neurodegenerative diseases involves transplanting neural stem cells into the first brain to replenish lost neurons. Harvesting these cells from the brain or spinal cord is difficult. Neural stem cells have been found in the second brain of human adults.5 These cells could be harvested using a simple endoscopic gut biopsy. This could provide a ready source of neural stem cells. One research team is planning toed them to treat diseases including Parkinson’s.

1Young, E. (2012). Alimentary thinking. New Scientist, 15 December, 39-42.

2American Journal of Gastrointestinal and Liver Physiology, vol 283, p G217.

3The British Journal of Psychiatry, vol 189, p.282.

4The Journal of Clinical Investigation, vol 121, p. 3094.

5Cell Tissue Research, vol 344, p.217.