Dirk Hanson, MA – Brain Blogger http://brainblogger.com Health and Science Blog Covering Brain Topics Wed, 30 May 2018 15:00:03 +0000 en-US hourly 1 https://wordpress.org/?v=4.9.6 Ambien, Sonata, and Lunesta – The Morning After http://brainblogger.com/2011/06/11/ambien-sonata-and-lunesta-the-morning-after/ http://brainblogger.com/2011/06/11/ambien-sonata-and-lunesta-the-morning-after/#comments Sat, 11 Jun 2011 12:00:43 +0000 http://brainblogger.com/?p=6645 The latest generation of sleep hypnotics — Ambien (zolpidem), Sonata (zaleplon), and Lunesta (zopiclone) — have introduced new terms into the American lexicon. We now speak of people “sleep-driving” under the influence of these medications, for instance. The official guide that comes with Lunesta, to take one example, warns of the side effects this way:

You may get up out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night.

Other than alcohol, sleep aids do not regularly cause unconscious behaviors like “driving a car, making and eating food, talking on the phone, having sex, sleep-walking.” That’s quite a list. And that is a lot of activity at night for a drug people are taking to help them sleep longer and deeper without waking making them drowsy the next morning. Seniors are also a prime user group of this type of drug — changes in sleep patterns naturally occur with age, making insomnia more of a problem among the elderly. Roughly 10-15% of the elderly population use hypnotic medications as sleep aids, says a report in Human Psychopharmacology.

According to the New York Times, prescriptions for Ambien made it the top drug in its class by 2006. The Big 3 “hypnosedatives” are closing the gap on benzodiazepines like Valium, the traditional class leader for sleep medication. Physicians wrote roughly an equal number of prescriptions for the newer hypnosedatives as they did for the classic benzodiazepine family by that year. Now a recent study in Psychopharmacology of older prescription drug users has confirmed that there is an additional threat of significant morning-after impairments. French researchers at the University of Caen School of Medicine road-tested a group of seniors using simulated driving scenarios, and found that each morning after taking one of the Big Three hypnotics, the subjects made more mistakes than placebo drivers when it came such measurements as speed and the detection of road exits.

The authors strongly suggest that better patient monitoring and instruction could dramatically cut back on the incidence of traffic accidents due to these prescription medications. But so far, there is no warning sticker for the pills that says:

Do not drive or operate heavy equipment after you wake up (You may have already been doing it in your sleep the night before).

It may seem obvious, but the morning-after impairment among older peole was a bit surprising, given that several earlier studies had not shown major cognitive deficits still at work by the 12-hour mark. The current study was small — 16 subjects over 55 years of age. However, as the first study to document significantly impaired driving in ageing drivers the morning after using Ambien or a similar drug, additional investigations of this effect become even more urgent.

Finally, there is one other matter to bear in mind when using hypnosedative drugs in older populations. A report in CNS Drugs says that common antibiotics like erythromycin, and other drugs like Tagamet (an ulcer drug) and Ketoconazole (a common fungus cream), may interfere with how the drugs work. And, as you probably could have guessed, mixing alcohol with these hypnosedatives is a ticket to even greater sedation and unanticipated interactions.

References

Bocca ML, Marie S, Lelong-Boulouard V, Bertran F, Couque C, Desfemmes T, Berthelon C, Amato JN, Moessinger M, Paillet-Loilier M, Coquerel A, & Denise P (2011). Zolpidem and zopiclone impair similarly monotonous driving performance after a single nighttime intake in aged subjects. Psychopharmacology, 214 (3), 699-706 PMID: 21086117

Hesse, L., von Moltke, L., & Greenblatt, D. (2003). Clinically Important Drug Interactions with Zopiclone, Zolpidem and Zaleplon CNS Drugs, 17 (7), 513-532 DOI: 10.2165/00023210-200317070-000042.

Otmani, S., Demazières, A., Staner, C., Jacob, N., Nir, T., Zisapel, N., & Staner, L. (2008). Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers Human Psychopharmacology: Clinical and Experimental, 23 (8), 693-705 DOI: 10.1002/hup.980

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Does This Light Make Me Fat? http://brainblogger.com/2011/02/20/does-this-light-make-me-fat/ http://brainblogger.com/2011/02/20/does-this-light-make-me-fat/#respond Sun, 20 Feb 2011 12:00:59 +0000 http://brainblogger.com/?p=6118 In 2003, a group of Italian university scientists and public health officials began sifting through the health records of shift workers at a factory in Apulia, Italy. The scientists had designed a cross-sectional study of 319 male workers with normal glucose and insulin levels, and were looking for metabolic and cardiovascular risk factors. Their study, published in the International Journal of Obesity, showed that workers on the night shift at the factory were significantly more likely to gain weight and show increases in systolic blood pressure than day workers.

“The prevalence of obesity was higher among shift workers compared to day workers,” the researchers found, “whereas body fat distribution was not different between the two groups.” The investigators concluded that “shift working was associated with BMI, independently of age and work duration.”

We know that diet, calories, and exercise are key determinants of obesity. But too much food and a lack of physical activity aren’t the whole story, as genetic studies have begun to demonstrate. And now, evidence is mounting that environmental factors play a role as well. One of the puzzling aspects of obesity is the tendency for some overweight people to snack heavily on high-carbohydrate foods at night. Years ago, Richard and Judith Wurtman, a husband and wife research team at the Massachusetts Institute of Technology (MIT) warned that the consumption of excessive snack carbohydrates at night might be “leading to severe obesity” in a form that very much resembled “a kind of substance abuse.”

Light is what powers our circadian clocks, and prior studies with mice have shown that mutations in so-called “clock” genes make the animals more susceptible to obesity and other metabolic disturbances. Laura Fonken, Joanna Workman, and others at Ohio State University and at the University of Haifa in Israel undertook a study of mice designed to determine the relationship between weight gain and extra light at night. Writing in the Proceedings of the National Academy of Sciences, the researchers found that mice housed for eight weeks under either bright lights or dim lights during the night “have significantly increased body mass and reduced glucose tolerance compared with mice in a standard light/dark cycle, despite equivalent levels of caloric intake and total daily activity output.”

Neuroscientist Laura Fonken told DiscoveryNews, “With the advent of electrical lighting at the turn of the 20th century, individuals of many species, including humans, became exposed to bright and unnatural light at night.” This technological development, Fonken and others believe, may be one of the driving forces behind epidemic levels of obesity in the U.S. and elsewhere.

What Fonken and the others had discovered was that “nighttime illumination at a level as low as 5 lx is sufficient to uncouple the timing of food consumption and locomotor activity, resulting in metabolic abnormalities.”

The study drew a blizzard of press coverage, in which the tempting leap from mouse studies to human eating behavior was undertaken at a dead run. How much can this really matter to humans? Potentially, quite a bit. As the researchers note, even brief circadian misalignment in humans can lead to “adverse metabolic and cardiovascular consequences.”

“Something about light at night was making the mice in our study want to eat at the wrong times to properly metabolize their food,” said Randy Nelson of Ohio State, a co-author of the study. Here’s what happened: The light-at-night mice, normally nocturnal feeders, switched partially to day feeding. “When we restricted their food intake to times whey they would normally eat, we didn’t see the weight gain,” according to Fonken. Eating at odd times in the circadian cycle disrupted the metabolism of the light-at-night mice — just as it disrupted the metabolism of the Italian shift workers — and the mice gained weight. “This further adds to the evidence that the timing of eating is critical to weight gain,” Fonken said.

Co-author Nelson summed up the results: People who stay up late and eat at night “may be eating at the wrong times, disrupting their metabolism. Clearly, maintaining body weight requires keeping caloric intake low and physical activity high, but this environmental factor may explain why some people who maintain good energy balance still gain weight.”

References

Arble DM, Bass J, Laposky AD, Vitaterna MH, & Turek FW (2009). Circadian timing of food intake contributes to weight gain. Obesity (Silver Spring, Md.), 17 (11), 2100-2 PMID: 19730426

Di Lorenzo L, De Pergola G, Zocchetti C, L’Abbate N, Basso A, Pannacciulli N, Cignarelli M, Giorgino R, & Soleo L (2003). Effect of shift work on body mass index: results of a study performed in 319 glucose-tolerant men working in a Southern Italian industry. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 27 (11), 1353-8 PMID: 14574346

Fonken LK, Workman JL, Walton JC, Weil ZM, Morris JS, Haim A, & Nelson RJ (2010). Light at night increases body mass by shifting the time of food intake. Proceedings of the National Academy of Sciences of the United States of America, 107 (43), 18664-9 PMID: 20937863

Ha M, & Park J (2005). Shiftwork and metabolic risk factors of cardiovascular disease. Journal of occupational health, 47 (2), 89-95 PMID: 15824472

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When Bipolar Patients Abuse Drugs – The Dual Diagnosis Dilemma http://brainblogger.com/2010/09/01/when-bipolar-patients-abuse-drugs-the-dual-diagnosis-dilemma/ http://brainblogger.com/2010/09/01/when-bipolar-patients-abuse-drugs-the-dual-diagnosis-dilemma/#comments Thu, 02 Sep 2010 00:59:49 +0000 http://brainblogger.com/?p=5345 Most people familiar with public health issues are aware of the challenges posed by “dual diagnosis” patients — those with both a psychiatric diagnosis and a substance abuse diagnosis. But the special case of addicted bipolar disorder patients is particularly problematic. Writing in the August issue of Current Psychiatry, Bryan K. Tolliver lists the severe outcomes that plague the victims of bipolar disorder who are also substance abusers: “Poor treatment compliance, longer and more frequent mood episodes, more mixed episodes, more hospitalizations, more suicide attempts.”

In Bipolar Disorders, Cassidy and coworkers conclude that lifetime rates of substance abuse in test populations of bipolar patients can run as high as 48.5% for alcohol and 44% for drugs. In addition, a study published in Psychiatric Services, which sampled almost 3,000 veterans diagnosed with bipolar disorder, found more evidence for troubling correlations: “Patients diagnosed as having both an alcohol use disorder and polysubstance dependence and who also were separated from their spouse or partner had a 100% risk of psychiatric hospitalization [Italics added]; risk of psychiatric hospitalization decreased to 52% if the patients were not separated from their partner.”

Not a pretty picture.

What is the link between these two seemingly disparate conditions? Why do bipolar disorder patients abuse alcohol and other drugs at rates far higher than other populations of psychiatric patients, or the population at large? In his article, professor Tolliver, who is with the clinical neuroscience division at the Medical University of South Carolina, lists several theories, along with their limitations:

Drug abuse as self-medication for an existing bipolar disorder. This explanation is often invoked to explain the very high rates of cigarette smoking among schizophrenics. However, it fails to account for the fact that manic depressives often use stimulant drugs when they are manic, and sedating drugs when they are depressed, rather than the other way around.

Co-morbidity as the result of common genetic risk factors. A compelling hypothesis, but, according to Tolliver, specific evidence in the form of genetic linkage studies is lacking.

Drug abuse as a symptom of bipolar disorder. The problem with this explanation is simply that most bipolar disorder patients do not have drug problems. And, in those that do, there is a “poor correlation of onset.”

Drug abuse as a trigger for bipolar disorder. In this case, the counter-evidence is that “emergence of mania before substance use disorder is common.” However, when the onset of mania precedes the development of drug abuse, particularly during adolescence, it “may predict a more severe course of both illnesses,” writes Tolliver.

Misdiagnosis based on common symptoms and “poor diagnostic boundaries.” But in this case we find that a high rate of drug abuse is common in longitudinal studies of patients initially hospitalized for mania.

There are other diagnostic problems. For example, procedures for bipolar clinical studies and drug trials often mean that patients with drug problems are routinely excluded. Similarly, patients with serious mental illnesses are themselves excluded from randomized controlled trials in substance abuse treatment studies.

Another common problem is that “denial of illness is a critical symptom that may fluctuate with disease course in both disorders.”  Furthermore, there can be clinical confusion when bipolar disorder “is overdiagnosed in persons engaged in active substance abuse or experiencing withdrawal.”

There is no FDA-approved pharmaceutical treatment for co-occurring bipolar disorder and substance abuse.  To make matters worse, drug abuse in bipolar disorder patients, especially rapid cyclers, usually predicts that the patient will have a poor response to lithium, the most common treatment for bipolar disorder.

Limited drug studies have been done, but thus far, few compounds have emerged as heavyweight candidates. Depakote,  (divalproex sodium), which is another common treatment for the manic phase of bipolar disorder, decreased the number of heavy drinking days in dual diagnosis patients when combined with lithium. But in a different study, the group differences petered out after six months. (Lithium alone was associated with decreases in cannabis use.) Carbamazepine, an anti-convulsant with a mixed history when used for cocaine dependence, seemed to slow cocaine use in one study of bipolar disorder patients. And Seroquel (Quetiapine), a controversial drug used in the treatment of schizophrenia, lessened some symptoms of depression. Finally, Revia (naltrexone), in a 12-week study of alcoholic patients with diagnosed with bipolar disorder, led to modest decreases in the number of drinking days.

None of these results can be characterized as a breakthrough, to say the least.  Integrated group therapy, designed specifically for dual diagnosis patients, has shown promise, compared to standard group drug counseling. But the reality is that additional research on treatment avenues is urgently needed for this most challenging of dual diagnosis disorders.

Resources

Tolliver, BK (2010). Bipolar Disorder and Substance Abuse. Current Psychiatry, 9 (8).

Cassidy F, Ahearn EP, & Carroll BJ (2001). Substance abuse in bipolar disorder. Bipolar disorders, 3 (4), 181-8 PMID: 11552957

Hoblyn JC, Balt SL, Woodard SA, & Brooks JO 3rd (2009). Substance use disorders as risk factors for psychiatric hospitalization in bipolar disorder. Psychiatric services (Washington, D.C.), 60 (1), 50-5 PMID: 19114570

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Drugs for Bulimia http://brainblogger.com/2010/08/02/drugs-for-bulimia/ http://brainblogger.com/2010/08/02/drugs-for-bulimia/#comments Mon, 02 Aug 2010 12:00:42 +0000 http://brainblogger.com/?p=5243 The word comes from the Greek “boulimia,” for bous (ox) plus limos (hunger).  Bulimia is ox hunger, which could mean something like “hungry as a horse.” In practice, it means “to gorge.” It is also known as bulimia nervosa, or binge-purge syndrome.  Bulimia is a disorder marked by the consumption of large amounts of food over a short period of time, followed by “compensatory behavior,” usually in the form of vomiting, to rectify this loss of control.  It is often grouped with anorexia, and while the two conditions share many symptoms –abnormal food consumption patterns, body image distortion, anxiety — none is stranger than the ailment clinicians have dubbed “body dysmorphic disorder” or BDD. People with this disorder feel deeply unattractive because of a perceived flaw in skin, hair, or facial features — minor flaws at best, or defects which demonstrably are not there — and cannot be reasoned out of this core belief. What they see in the mirror is simply different from what others objectively see about them.

There are also significant differences between the two eating disorders. Recent brain imaging work has shown that bulimia and anorexia show different activity in the frontal, cingulate and parietal cortical regions.  Other studies have shown that bulimics exhibit low endogenous levels of serotonin at 5-HT receptor and transporter sites.

Bulimics show more activity than non-bulimics or other binge eaters in the nucleus accumbens—a prime site of action for addictive drugs — when they are shown tasty food, such as cakes.  Moreover, for many bulimics there is a definite “high,” which comes with the purging, and which has no analogue in anorexia. Bulimia’s impact on the brain’s reward center also seems to be quite direct, judging by the high relapse rates of bulimics.

All of this suggests that bulimics are overly sensitive to certain kinds of food, in the same way that drug addicts are hypersensitive to the reward aspect of certain kinds of drugs. The fact that bulimics (and alcoholics, and heroin addicts) have a tendency to binge on high carbohydrate foods rich in tryptophan, serotonin’s precursor chemical, is well documented. Richard Wurtman and coworkers at MIT identified a subset of bulimics who binge severely on carbohydrate foods. These bulimics tended to be mildly obese, severely depressed, and came from families with a strong history of alcohol abuse. Other researchers have reported that a significant number of bulimics are themselves abusers of alcohol and other drugs.

The first major breakthrough in the treatment of bulimia came with the era of SSRI antidepressant medications.  The initial motivation was a perceived link between bulimia and depression, which commonly exist as co-morbid disorders.  Serotonin was clearly involved in some way in the mechanisms of active bulimia. In 1997, Prozac became the first drug ever licensed by the FDA for the treatment of bulimia nervosa. The drug’s formal approval was based on clinical studies showing median reductions in binging of as much as 67 per cent for Prozac, compared with 33 per cent for placebo. Vomiting was reduced by 56 per cent, compared to 5 per cent for female placebo users. (About 10 per cent of diagnosed bulimics are males.)  While cure is too strong a word, the benefits were quite dramatic in some cases.

What about the roughly 50% of bulimics who do not respond to serotonin-boosting medications? Recent research covered by the science blog Neurotopia points the finger at a long nerve running through the cranium.  The tenth cranial nerve, better known as the vagus nerve, branches through the neck, thorax and abdomen, and is involved in breathing, tasting, swallowing, and digestion. Most of the signal traffic carried by the vagus nerve is one way: from the body to the brain. Suspicion fell on the vagus nerve because of its direct involvement with one of bulimia’s most salient traits — the inability to feel normal levels of fullness, or satiety.

Bulimics must eat more at a sitting than non-bulimics in order to feel satisfied.  There is evidence of vagus nerve involvement in meal satiation, portion size, and, notably, control of vomiting. Researchers have suggested that bulimics have a relatively insensitive vagus nerve, made even less sensitive by the debilitating cycle of overeating and vomiting. Hence, bulimia patients need greater vagus nerve stimulation in order to stop eating.  Interestingly, studies have also shown that people suffering from bulimia have high pain thresholds, compared to non-bulimics.

This dysregulation of the vagus nerve responds to the drug ondansetron, according to recent research published in Physiology & Behavior by Patricia L. Faris and colleagues. The antiemetic effects of ondansetron, which reduce vagus nerve activity by acting on the 5-HT3 serotonin receptor, seem to decrease vomiting while increasing the number of normal meals eaten.

Finally, a third path toward treatment has been sparked by research on opioid receptors. Decreased endogenous opioid activity may also underpin bulimia. A small 2005 study by Johns Hopkins University School of Medicine analyzed the results of brain MRIs on eight bulimic women and eight controls. Bulimics showed decreased opioid receptor binding in the insula, another area of the brain implicated in MRI studies of addiction. The insula has been called the brain’s “gustatory cortex,” and it may be that the repeating cycle of binge and purge activates the opioid system. Opioid receptors are involved in the processing of the reward value of food. This suggests that a drug like naltrexone, which blocks opiate receptors, might also have a role to play in the treatment of bulimia.

References

Bencherif B, Guarda AS, Colantuoni C, Ravert HT, Dannals RF, & Frost JJ (2005). Regional mu-opioid receptor binding in insular cortex is decreased in bulimia nervosa and correlates inversely with fasting behavior. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 46 (8), 1349-51 PMID: 16085593

FARIS, P., HOFBAUER, R., DAUGHTERS, R., VANDENLANGENBERG, E., IVERSEN, L., GOODALE, R., MAXWELL, R., ECKERT, E., & HARTMAN, B. (2008). De-stabilization of the positive vago-vagal reflex in bulimia nervosa Physiology & Behavior, 94 (1), 136-153 DOI: 10.1016/j.physbeh.2007.11.036

KAYE, W., FRANK, G., BAILER, U., HENRY, S., MELTZER, C., PRICE, J., MATHIS, C., & WAGNER, A. (2005). Serotonin alterations in anorexia and bulimia nervosa: New insights from imaging studies Physiology & Behavior, 85 (1), 73-81 DOI: 10.1016/j.physbeh.2005.04.013

Schienle, A., Schäfer, A., Hermann, A., & Vaitl, D. (2009). Binge-Eating Disorder: Reward Sensitivity and Brain Activation to Images of Food Biological Psychiatry, 65 (8), 654-661 DOI: 10.1016/j.biopsych.2008.09.028

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Trick of the Light – Optical Illusions Can’t be Beat http://brainblogger.com/2010/06/06/trick-of-the-light-optical-illusions-can%e2%80%99t-be-beat/ http://brainblogger.com/2010/06/06/trick-of-the-light-optical-illusions-can%e2%80%99t-be-beat/#comments Sun, 06 Jun 2010 12:00:55 +0000 http://brainblogger.com/?p=5033 You know ‘em, you love ‘em: Suddenly, pictures bulge out in three dimensions, or static dots begin to swirl, or you see colors that aren’t really there. Tricking your eye is as easy as the well-known “finger sausage” maneuver: Hold out your arms, point your index fingers toward each other, then move them slowly together while gazing at a loosely focused spot behind them. Suddenly, a floating blimp appears between the two fingers. It isn’t there. But there it is. (A phenomenon known to neuroscientists as “cognitive impenetrability.”)

Neuroscientists who specialize in visual perception have long recognized that everything we see is, in essence, an optical illusion. But the illusions we are referring to here are cases where the brain’s subjective perception of a visual image is out of kilter with the physical world. That’s part of their charm. It would not be outlandish to suggest that brain science received an early push from the effort to decode the painterly visual tricks that the 17th and 18th Century masters were able to achieve by brushstroke. The illusions produced by skilled painters were proof that what we see is not always what is there to be seen. Some early painters delighted in a style called trompe l’oeil, French for “trick the eye.” (The practice lives on in Holland, where urinals in men’s public bathrooms often sport a lifelike graphic of a housefly, which, when aimed at — and who does not — makes life easier for restroom custodians.)

However, there is more to this category of illusions than mere amusement. It was Aristotle who first noted that the act of staring at a waterfall for several minutes would cause nearby objects to appear to float upwards. A related illusion, the “flash lag effect,” may affect the outcome of sporting events, for example by influencing a judge’s perception of where a ball touches the ground.  Visual illusions are even employed in highway design, in cases where traffic engineers call for road stripes to be painted closer and closer together as a curve becomes sharper. The idea is that drivers will be fooled by the illusion into thinking that they are speeding up, and will slow down as a result.

Optical illusions represent one of those fertile fields where science meets art. Escher’s “Ascending and Descending” artwork, and the “impossible staircase” drawing by mathematician Roger Penrose were conceived within two years of each other.  Illusions come in a variety of categories: motion, luminance, contrast, color, 3D interpretation, and gestalt effects, for starters. One common set of illusions involves size constancy—comparing two squares and picking the larger one, for example. This illusions stems from the innate tendency of the visual system to “multiply retinal (or angular) size with assumed distance, enabling us to estimate size independent of geometrical perspective,” according to ophthalmologists Michael Bach and Charlotte Poloschek in Advances in Clinical Neuroscience and Rehabilitation.  We possess this ability from birth, and only notice it when it fails, as when the moon appears larger near the horizon.

In fact, optical illusions are not really “optical” at all. In general, they do not result from physical properties of the eye, or the abnormal activation of rods and cones. Optical illusions are truly formed in the “mind’s eye.” They are visual illusions. Consider, as an easy example, the results of a hard blow to the head. Those lights you see aren’t “optical” at all. No actual spots or streaks of light enter your eyes. Instead, the brain incorrectly interprets one of the results of the blow — the mechanical activation of neurons in the eye — as “light.”

In an fMRI study of subjects observing a classic illusion called “Rotating Snakes,” in which a static picture induces the illusion of smooth motion when stared at, researchers determined that the illusion activated motion sensitive areas of the primary visual cortex — but that the effect appeared to be dependent upon “some component of eye movements.” When people moved their eyes while looking at the illusion, the motion detection areas of the visual cortex lit up. No eye movement, no illusion.

Is there a possible evolutionary explanation for these gaps in our visual intelligence? Neurobiologist Mark Changizi at Rensselaer Polytechnic Institute told ABC News that visual illusions are one way the brain attempts to “see into the future” as a means of enhancing survivability. Visual illusions are produced in the split-second interval between light reaching the retina, and the brain’s translation of that retinal image into a visual perception, “Illusions occur when the brain attempts to perceive the future,” says Changizi, “and those perceptions don’t match reality.”

Another theory takes as its starting point the limitations on the amount of input a brain can effectively process — only so many neuronal connections; only so many ways to transmit data. But the potential optical information out there for the processing is practically infinite. Visual illusions may be one result of the way the brain attempts to take shortcuts; to delimit the vast amount of incoming perceptions. The brain’s visual processing structures make inferences, fill in the blanks, and resort to default estimations based on normal rules of perception. The results can sometimes be erroneous.

As it turns out, you can trust your eyes. Your eyes are fine. However, you cannot trust the primary visual cortex in your brain. When it comes to what the eye sees, humans must accept the fact that the brain is prone to leaping to conclusions. It makes inferences, fills in gaps, and draws conclusions — all of which, in the case of visual illusions, turn out to be incorrect.

References

Bach, M., Poloschek, C.M. (2006). Optical Illusions. Advances in Clinical Neuroscience and Rehabilitation, 6, 20–21.

Kuriki I, Ashida H, Murakami I, & Kitaoka A (2008). Functional brain imaging of the Rotating Snakes illusion by fMRI. Journal of vision, 8 (10), 16-10 PMID: 19146358

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Speaking in Tongues – A Neural Snapshot http://brainblogger.com/2010/02/07/speaking-in-tongues-a-neural-snapshot/ http://brainblogger.com/2010/02/07/speaking-in-tongues-a-neural-snapshot/#comments Sun, 07 Feb 2010 12:00:41 +0000 http://brainblogger.com/?p=3810 “Asaria isa asaria ari masheetee sadabada vena amina gotaya menda meshela mosha nami ki toro ma…”

Glossolalia, or speaking in tongues, has fascinated thinkers ever since the “tongues of angels” descended upon early believers as a gift from the Holy Ghost in the New Testament of the Bible. This unusual mental state, characterized by utterances that sometimes sound like an untranslated psalm from Mars, typically occurs during instances of religious excitation, and is primarily associated with Pentecostal religious practices. It has commonly been considered a form of ecstatic trance accompanied by verbal utterances not found in any language.

Tongue speakers typically claim that the outbursts are non-voluntary, but others can sometimes produce instances of glossolalia on demand. Glossolalia has typically been considered a psychopathology, although little has been known about what occurs in the brain during this behavior. Plato asserted that these occurrences were caused by divine inspiration. He suggested that God took possession of the mind while man was sleeping or possessed, and during such a state, God inspired man with utterances that he can neither understand nor interpret.

Research performed in the 1980s at Denison University by the late anthropologist Felicitas Goodman led to a theory that glossolalia was a trance state caused by rhythmic discharges from the reticular formation, an area of the brain stem that plays a role in sleep and dreams. Goodman believed that this represented an alternative neural pathway for language, but more recent research has cast light on activity in other areas of the brain.

In 2006, Andrew Newberg and associates conducted the first functional neuroimaging study of cerebral changes during the act of glossolalia. In the study, published in Psychiatry Research: Neuroimaging, Newberg and other researchers at the University of Pennsylvania managed to run single photon emission computed tomography (SPECT) scans to measure regional cerebral blood flow in the brains of five people during episodes of active glossolalia. (As controls, the investigators took scans of people singing gospel songs.)  Despite the prevailing notion in the biomedical community of glossolalia as psychopathology, the researchers discovered that “the limited number of reported studies have suggested that people who speak in tongues show no differences in personality traits from other population groups.” Indeed, an earlier study in Britain of glossolalia among the clergy found that those who sometimes spoke in tongues showed more emotional stability and less depression than a control group.

In an earlier neuroimaging study of meditation states, Newberg and coworkers had observed increased activity in the frontal lobes, a finding consistent with scans of other attention-focusing activities.  But in the case of glossolalia, Newberg, the director for the Center for Spirituality and the Mind at the University of Pennsylvania School of Medicine, discovered that activity the frontal lobes decreased, including activity in the brain’s primary language processing centers: “Our finding of decreased activity in the frontal lobes during the practice of speaking in tongues is fascinating because these subjects truly believe that the spirit of God is moving through them and controlling them to speak. Our brain imaging research shows us that these subjects are not in control of the usual language centers during this activity, which is consistent with their description of a lack of intentional control while speaking in tongues.”

Another area of activity during glossolalia is the left superior parietal lobe (SPL), a region behind the frontal lobes that plays an important role in processing sensory input. In the meditation scans, during which subjects describe a loss of the sense of self, there was a significant decreases in SPL activity. However, glossolalia patients showed no such decreases, a finding consistent with their assertion that they experience no loss of individual boundaries, or submerging of the sense of self, while speaking in tongues.

The study also found increased activity in the limbic system, the seat of emotional responses, but the researchers declined to speculate on “altered emotional activity during glossolalia.”

One of the curious aspects of the study, as pointed out on the Neurocritic Blog, is that the subjects were capable of entering the state of glossolalia more or less on cue. This finding seems to call into question the “spontaneous utterance” aspect of glossolalia.

Spiritual or religious aspects notwithstanding, the study strongly points to the act of speaking in tongues as a verifiable language phenomenon that invites further study.

References

Francis, L. (2003). Personality and Glossolalia: A Study Among Male Evangelical Clergy Pastoral Psychology, 51 (5), 391-396 DOI: 10.1023/A:1023618715407

Goodman, Felicitas D. (1969). Phonetic Analysis of Glossolalia in Four Cultural Settings. Journal for the Scientific Study of Religion, 8 (2), 227-239.

NEWBERG, A., WINTERING, N., MORGAN, D., & WALDMAN, M. (2006). The measurement of regional cerebral blood flow during glossolalia: A preliminary SPECT study Psychiatry Research: Neuroimaging, 148 (1), 67-71 DOI: 10.1016/j.pscychresns.2006.07.001

Richardson, James T. (1973). Psychological Interpretations of Glossolalia: A Reexamination of Research. Journal for the Scientific Study of Religion, 12 (2), 199-207.

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The Evolution of Depression http://brainblogger.com/2009/11/10/the-evolution-of-depression/ http://brainblogger.com/2009/11/10/the-evolution-of-depression/#comments Wed, 11 Nov 2009 04:58:49 +0000 http://brainblogger.com/?p=3411 Millions of people around the world suffer from depression, the most common mental disorder of all. Since depression appears to be largely genetic, several long-standing questions continue to bedevil researchers. Have the genes for clinical unipolar depression undergone selective evolution–or is depression a random product of mutation, evolutionary drift, or other non-selective forces?

The symptoms of depression are found in every culture and time period, from the ancient Greeks to modern New Yorkers, from the !Kung of southern Africa to ranchers in the American West. Why is depression so much more common than any other major mental illness? Clearly, it is a malfunction, a maladaptation — or is it?

What if depression sometimes turns out to be a useful adaptation, rather than a malfunction?  When people are depressed, they spend more time thinking, and less time engaged in physical activity. Paul W. Andrews, a researcher with the Virginia Institute for Psychiatric and Behavioral Genetics at Virginia Commonwealth University, believes that “depression is an evolved emotional response to complex problems, and its function is to promote changes in body systems that promote analysis of those problems.”

In a recent paper for Psychological Review — “The bright side of being blue” — Paul Andrews and Anderson Thomson propose the “analytical rumination hypothesis” to explain the widespread occurrence of depression. As an evolved response to solving complex problems, depression’s function is to “minimize disruption and sustain analysis of those problems by… reducing the desire to engage in distracting activities (anhedonia), and producing psychomotor changes that reduce exposure to distracting stimuli.”

Writing for ScientificAmerican.com, the two researchers argued that depression involves a specific, highly analytical thinking style.  Faced with a difficult math problem, “feeling depressed is often a useful response that may help you analyze and solve it,” the authors write. They claim to have found evidence that “people who get more depressed while they are working on complex problems in an intelligence test tend to score higher on the test.”

The authors point to various lab experiments indicating that depressed people may be better at solving complex social dilemmas as well, because they give more scrutiny to the costs and benefits of various options. What may look like indecision, or an inability to act decisively, may be artifacts of a particular problem-solving style; a cognitive technique that requires a minimum of outside distractions.

Viewed in this light, certain symptoms of depression — social isolation, an inability to derive pleasure from pleasurable acts (like sex), and a loss of appetite — combine to maximize the brain’s ability to focus and process information. This combination of cognitive and psychomotor effects might have the adaptive function of putting the brain in the perfect gear for certain kinds of complex problem solving.

The theory is far from watertight. Yes, depressives are capable of monumental feats of rumination and contemplation. But is obsessive brooding always a fruitful technique? As anyone who has dealt with a depressed person knows, the conclusions reached by all this high-level problem solving are often completely erroneous.  In many cases, depressives seem to be even more prone to fallacious thinking than non-depressed problem solvers.

The debate over the usefulness of depression shows no signs of early or easy resolution. But the search for the adaptive significance of mental and emotional traits always carries with it the possibility of major insights into evolutionary biology.

References

Andrews, P., Thomson Jr., J. (2009). Depression’s Evolutionary Roots. Mind Matters, August 25, scientificamerican.com.

Andrews, P., & Thomson, J. (2009). The bright side of being blue: Depression as an adaptation for analyzing complex problems. Psychological Review, 116 (3), 620-654 DOI: 10.1037/a0016242

Watson, P. (2002). Toward a revised evolutionary adaptationist analysis of depression: the social navigation hypothesis Journal of Affective Disorders, 72 (1), 1-14 DOI: 10.1016/S0165-0327(01)00459-1

Hertel, Jochen Neuhof, Thomas Theue, G. (2000). Mood effects on cooperation in small groups: Does positive mood simply lead to more cooperation? Cognition & Emotion, 14 (4), 441-472 DOI: 10.1080/026999300402754

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Hearing Voices – Underpinnings of Auditory Hallucinations http://brainblogger.com/2009/09/22/hearing-voices-underpinnings-of-auditory-hallucinations/ http://brainblogger.com/2009/09/22/hearing-voices-underpinnings-of-auditory-hallucinations/#comments Tue, 22 Sep 2009 12:00:08 +0000 http://brainblogger.com/?p=3257 In “The Origin of Consciousness in the Breakdown of the Bicameral Mind,” Julian Jaynes suggested back in 1976 that schizophrenia — like spirit possession and imaginary playmates — was a vestige of our brain’s bicameral heritage. Jaynes believed that in man’s early history, the left and right hemispheres of the brain did not “talk” to each other. They failed to communicate effectively across the corpus callosum, the bridge from one hemisphere to another. The result was, to Jaynes, obvious: People used to hear voices. Nowadays, most people who hear voices inside their head are diagnosed as schizophrenics.

What exactly is going on in the brain during auditory hallucinations? And is the act of hearing voices inside one’s head always incontrovertible evidence of psychosis? In recent years, the use of MRIs, PET scans and other imaging technologies has given researchers some specific clues about these and other questions.

Auditory hallucinations are considered by many medical professionals to be the most frequent and reliable symptom of psychosis. More than 70 percent of diagnosed schizophrenics suffer from them at some point in the course of their disease. In Frontiers in Neuroscience, Kenneth Hugdahl and a group of researchers at the University of Bergen, Norway, published a recent study of temporal disturbances during auditory hallucinations. The main question the scientists sought to answer was whether there are identifiable brain tissue abnormalities in schizophrenic patients who frequently hear voices. And there are. Confirming earlier studies, Hugdahl’s group found significantly reduced grey matter density in the left peri-Sylvian region, an area of the cerebral cortex that includes Broca’s Area, Wernicke’s Area, and other language-processing structures. Lesions to the so-called peri-Sylvian region of the left superior temporal gyrus can cause loss of language capabilities. The researchers found that “hallucinating patients had significantly reduced grey matter density in the left superior temporal gyrus, the medial prefrontal cortex in peri-ventricular areas, and in the thalamus.”

In addition to identifying a pathology in the speech processing areas of the left temporal lobe of schizophrenics, the researchers suggested a specific mechanism for the abnormalities: low concentrations of glutamate. “We suggest that glutamatergic transmission may be deficient in auditory hallucinations which may trigger the experience of hearing voices,” the group at the University of Bergen concluded. Antipsychotic drugs like risperidone typically target dopamine receptors. Stimulating glutamate receptors as a treatment is still unproven. However, drug maker Lilly has been working on one such drug, known only as LY2140023, for several years.

Meanwhile, earlier work from Great Britain published in the American Journal of Psychiatry has also implicated a region in the right brain, specifically the right middle temporal gyrus, which responds to external speech. Normal people respond to external speech with greater left side activity. In schizophrenics, this region in the right brain is hyperactive, suggesting a possible compensatory increase due to left-hemisphere language processing dysfunctions. The Norwegian researchers suggested that “auditory hallucinations ‘compete’ with external speech for processing sites within the temporal cortex. This notion of competition is consistent with the use of listening to music or speech as a means of alleviating auditory hallucinations.” Such “attentional strategies” help many schizophrenics modulate the voices, and they also suggest ways of assessing specific therapeutic interventions for auditory hallucinations.

Most notably, the group of British researchers hypothesized that if such language dysfunction “has its origins in early brain development, it might be possible to detect abnormally lateralized auditory processes in children who will later develop schizophrenia.”

The past few years have also seen the development of a radical counter-movement that seeks to normalize the act of hearing voices. The movement is said to have originated in the Netherlands and the U.K. Intervoice, which bills itself as “the international community for hearing voices,” says they have found that many people who hear voices “are not troubled by them or have found their own ways of coping with them outside of psychiatric care.” Those voice hearers who are “overwhelmed by the negative and disempowering aspects of the experience” are often diagnosed as schizophrenics — “a harmful and stigmatizing concept,” in the opinion of Intervoice.

References

AGUILAR, E., SANJUAN, J., GARCIAMARTI, G., LULL, J., & ROBLES, M. (2008). MR and genetics in schizophrenia: Focus on auditory hallucinations European Journal of Radiology, 67 (3), 434-439 DOI: 10.1016/j.ejrad.2008.02.046

Woodruff, P., Wright, I., Bullmore, E., Brammer, M., Howard, R., et. al. (1997). Auditory Hallucinations and the Temporal Cortical Response to Speech in Schizophrenia: A Functional Magnetic Resonance Imaging Study. American Journal of  Psychiatry, 154, 1676-1682.

Barta, P., Pearlson, G., Powers, R., Richards, S., and Tune, L. (1990). Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. American Journal of Psychiatry, 147, 1457-1462.

Hugdahl, K., Loberg, E., Specht, K., Steen, V, Wageningen, H., and Jorgensen, H. (2008). Auditory hallucinations in schizophrenia: the role of cognitive, brain structural and genetic disturbances in the left temporal lobe. Frontiers in Human Neuroscience, 1, Article 6.

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Why Do Schizophrenics Smoke Cigarettes? http://brainblogger.com/2009/07/03/why-do-schizophrenics-smoke-cigarettes/ http://brainblogger.com/2009/07/03/why-do-schizophrenics-smoke-cigarettes/#comments Fri, 03 Jul 2009 13:30:44 +0000 http://brainblogger.com/?p=2979 Psychiatry and Psychology CategoryFor health care workers in psychiatric hospitals, it is no secret: one of the major issues confronting psychiatric facilities seeking to institute blanket no-smoking policies concerns chronic inpatients with schizophrenia. Patients with schizophrenia are almost always heavy cigarette smokers, given a choice. As Edward Lyon wrote in an analysis of studies and surveys performed throughout the 1990s: “Many patients in psychiatric hospitals would smoke two, three, or even four packs of cigarettes a day if an unlimited supply of cigarettes were available.”

Generally, the rate of inpatient smoking among schizophrenics is three to four times higher than the general smoking population. In one British study of 100 institutionalized schizophrenics cited by Lyon, 92% of the men and 82% of the women were smokers. Moreover, schizophrenics smoke more cigarettes per day than other smokers do, and they commonly smoke high-tar, unfiltered cigarettes — niche brands for heavy smokers used by only 1% of the total smoking population.

CigarettesAustralian research performed in 2001 found that because of high rates of smoking, “people with mental illness have 30% more heart disease and 30% more respiratory disorders,” according to Ann Crocker, now a professor of Clinical Psychiatry at McGill University.

Not only do an estimated 80% of schizophrenics smoke, compared to roughly 25% of the total adult population, psychiatric facilities report that depressives and those with anxiety disorders also smoke in great numbers.

Why?

The review of studies through 1999, undertaken by Lyon and published in Psychiatric Services, shows unequivocally that schizophrenic smokers are self-medicating to improve processing of auditory stimuli and to reduce many of the cognitive symptoms of the disease. “Neurobiological factors provide the strongest explanation for the link between smoking and schizophrenia,” Lyons writes, “because a direct neurochemical interaction can be demonstrated.”

Of particular interest is the interaction between nicotine and dopamine in the nucleus accumbens and prefrontal cortex.  Several of the symptoms of schizophrenia appear to be associated with dopamine release in these brain areas. A 2005 German study concluded that nicotine improved cognitive functions related to attention and memory. “There is substantial evidence that nicotine could be used by patients with schizophrenia as a ‘self-medication’ to improve deficits in attention, cognition, and information processing and to reduce side effects of antipsychotic medication,” the German researchers concluded.

In addition, the process known as “sensory gating,” which lowers response levels to repeated auditory stimuli, so that a schizophrenic’s response to a second stimulus is greater than a normal person’s, is also impacted by cigarettes.  Sensory gating may be involved in the auditory hallucinations common to schizophrenics. Receptors for nicotine are involved in sensory gating, and several studies have shown that sensory gating among schizophrenics is markedly improved after smoking.

There is an additional reason why smoking is an issue of importance for health professionals. According to Lyon, “Several studies have reported that smokers require higher levels of antipsychotics than nonsmokers. Smoking can lower the blood levels of some antipsychotics by as much as 50%…. For example, Ziedonis and associates found that the average antipsychotic dosage for smokers in their sample was 590 mg in chlorpromazine equivalents compared with 375 mg for nonsmokers.”

Smoking among inpatient psychiatric patients is not trivial. Neither is the decision to institute smoking bans in psychiatric hospitals, a move that is understandably unpopular with patients.

References

Lyon, E. (1999). A Review of the Effects of Nicotine on Schizophrenia and Antipsychotic Medications. Psychiatric Services, 50, 1346-1350.

Cattapan-Ludewig, K. (2005). Why do schizophrenic patients smoke? Nervenarzt, 76 (3), 287-294.

Mueser, K., Crocker, A., Frisman, L., Drake, R., Covell, N., & Essock, S. (2005). Conduct Disorder and Antisocial Personality Disorder in Persons With Severe Psychiatric and Substance Use Disorders Schizophrenia Bulletin, 32 (4), 626-636 DOI: 10.1093/schbul/sbj068

Adler, L., Hoffer, L. Wiser, A. (1993). Normalization of auditory physiology by cigarette smoking in schizophrenic patients. American Journal of Psychiatry, 150, 1856-1861.

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Marijuana Withdrawal Syndrome http://brainblogger.com/2009/06/15/marijuana-withdrawal-syndrome/ http://brainblogger.com/2009/06/15/marijuana-withdrawal-syndrome/#comments Mon, 15 Jun 2009 16:24:49 +0000 http://brainblogger.com/?p=2841 There are now several clinical trials showing that mice and dogs show evidence of cannabis withdrawal. (For THC-addicted dogs, it is the abnormal number of wet-dog shakes that give them away.) Today, scientists have a much better picture of the jobs performed by anandamide, the body’s own form of THC. This knowledge helps explain a wide range of THC withdrawal symptoms.

Among the endogenous tasks performed by anandamide are pain control, memory blocking, appetite enhancement, the suckling reflex, lowering of blood pressure during shock, and the regulation of certain immune responses. These functions shed light on common hallmarks of cannabis withdrawal, such as anxiety, chills, sweats, flu-like physical symptoms, and decreased appetite. At Columbia University’s National Center on Addiction and Substance Abuse, where a great deal of National Institute for Drug Abuse (NIDA) funded research takes place, researchers have found that abrupt marijuana withdrawal leads to symptoms similar to depression and nicotine withdrawal.

What the NIDA has learned about cannabis addiction, according to the principal investigator of a recent NIDA study, was that “we had no difficulty recruiting dozens of people between the ages of 30 and 55 who have smoked marijuana at least 5,000 times. A simple ad in the paper generated hundreds of phone calls from such people.” (This would be roughly equivalent to 14 years of daily pot smoking.)

Here is a sampling of comments from dependent marijuana smokers, gathered from my blog, Addiction Inbox :

Comment 1

I’m 55 and I’ve been smoking pot off and on for the last 30 years… I had no idea of the withdrawal I would experience. Two days in, I thought for sure I had some dreaded disease. One minute I would be freezing, the next sweating. The loss of appetite doesn’t bother me because pot always helped me keep on an extra 5-10 lbs from the munchies and sweet tooth. Not sure how long it will take, but I do look forward to the day when this has all passed.

Comment 2

As far as symptoms, the worst for me so far has been insomnia, on day nine I was awake for 28 hours, a hallucinatory experience itself….The temperature regulation thing is very real, I’m freezing, I’m burning, I’m sweating. Starting to get hungry once a day.

Comment 3

The cravings have pretty much subsided but not completely. When I get bored is when it is the strongest. I have experienced the sweating, severe diarrhea, migraine headaches and sleeplessness…. I have hidden this addiction from family for so long and it’s nice to not have to worry if someone is going to stop by and smell it and catch me.

Comment 4

I have been smoking pot since I was 17, I am now 34, happily married with a child. I smoked at least once a day, up to 4 joints a day by myself. I stopped smoking a week ago but I am completely miserable…. I am always dreaming of using, I wake up in sweats and search the whole house for a roach sometimes when I am desperate but at the same time I feel proud that I have not called my dealer or visited my using friends, this time I might as well do it.

Comment 5

It’s been 2 weeks since I vaporized my last bowl, and since then I’ve gotten so desperate I’ve been smoking resin. Last night I used rubbing alcohol to get the resin out of my bong and smoked the resin after the alcohol evaporated. It tasted awful and barely got me high, but tonight I did it again, and I was so impatient that I put the resin-alcohol solution in the oven to help it evaporate! This is how desperate I’ve become – I’ve risked burning down my house in order to get marginally high.

Comment 6

After using heavily for the past 7 years, and basically all day every day for the last 6 months my side effects are major. i still cant sleep properly although at least now im getting 6 hours which isnt too bad. nausea every day. i have a bad stomach to begin with but i usually dont get sick every day. hot and cold sweats. im freezing right now but about half an hour ago i was boiling. i havent eaten properly since i stopped. the thing i dont like is that i feel spaced out constantly. i feel like im bent even when im not. and not bent in a calm relaxing way either.

Comment 7

I am a researcher at a university and have studied the effects of drugs, particularly alcohol, on the brain for the last decade or so. Like many of my friends and colleagues, I consider marijuana to be a relatively low-risk drug when used in moderation by responsible adults. However, I am now forced to admit that my view of the discontinuation syndrome was naïve and that I was completely unprepared for it myself:

Week 1: Despite missing my evening smoking session and feeling some mild irritability, I felt fine.

Week 2: Mild flu-like symptoms, which I assumed to be viral in nature though it did not exactly feel viral. No real desire to smoke marijuana. I assumed I was out of the woods and had gotten off easy.

Week 3: Sudden onset of incredibly intense and vivid dreams. Profuse sweating at night. Difficulty discerning dreaming from waking state. Lack of energy. Upset stomach. Absolutely no appetite. Unable to focus. Saw my primary care physician. All labs normal.

Week 4: This is where the real problems began for me. Sudden onset of intense, full body anxiety…. This led to complete insomnia for days. A very deep feeling of dread and a sense that I was going completely insane. Crying spells that came from nowhere….

Week 5: The intense anxiety slowly began to dissipate… was able to sleep for 4-6 hours a night, which is approaching normal for me. Appetite slowly came back but the thought of eating was unpleasant. Feeling of confidence began to return. Feelings of hopelessness and of going crazy began to diminish.

References

Budney, A. (2004). Review of the Validity and Significance of Cannabis Withdrawal Syndrome American Journal of Psychiatry, 161 (11), 1967-1977 DOI: 10.1176/appi.ajp.161.11.1967

Lichtman, A.H. and Martin, B.R. (2002) Marijuana withdrawal syndrome in the animal model. Journal of Clinical Pharmacology, 42, 20S-27S.

Vandrey, R., Budney, A., Kamon, J., & Stanger, C. (2005). Cannabis withdrawal in adolescent treatment seekers Drug and Alcohol Dependence, 78 (2), 205-210 DOI: 10.1016/j.drugalcdep.2004.11.001

WILSON, D., VARVEL, S., HARLOE, J., MARTIN, B., & LICHTMAN, A. (2006). SR 141716 (Rimonabant) precipitates withdrawal in marijuana-dependent mice Pharmacology Biochemistry and Behavior, 85 (1), 105-113 DOI: 10.1016/j.pbb.2006.07.018

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Clearing the Haze – Is Marijuana Addictive? http://brainblogger.com/2009/05/19/clearing-the-haze-is-marijuana-addictive/ http://brainblogger.com/2009/05/19/clearing-the-haze-is-marijuana-addictive/#comments Tue, 19 May 2009 17:15:12 +0000 http://brainblogger.com/?p=2740 In the past few years, as addiction researchers have been mapping out the chemical alterations in the brain caused by alcohol, nicotine, methamphetamine, and other drugs, America’s most popular illegal drug has remained largely a scientific mystery. It is a drug that millions of Americans have been using regularly for years, and, from a clinical perspective, it remains the least studied illicit drug of all.

The most popular, and the least studied — not a prescription for rational decision making from a public health point of view. A variety of influences combined to force marijuana research off the table years ago, but the birth of “receptorology,” as molecular scientist Candace Pert once called it, and a more relaxed grip on federal funding has refueled the research.

Why did cannabis research lag behind that of other drugs of abuse? For decades, the prevailing belief among users and clinical researchers alike was that marijuana did not produce dependency and therefore could not produce major withdrawal symptoms. Nonetheless, heavy marijuana users were claiming that tolerance does build. And when they withdraw from use, many report strong cravings. Marijuana withdrawal, which typically affects only heavy smokers, has not been well characterized by the research community.

Back in the fall of 1988, pharmacology professor Allyn Howlett and her colleagues at St. Louis University Medical School came up with strong evidence for the specific brain receptor to which the THC molecules were binding. However, the nature of the organic chemical itself — the compound in the brain that was meant to bind to those reported sites — remained unidentified until 1992. That year, William A. Devane, one of the researchers at Hebrew University in Jerusalem, along with Rafael Mechoulam and others, identified the body’s own form of THC in pulverized pig brains. The substance that stuck to the THC receptors was known as arachidonyl ethanolamide. Devane christened the substance “anandamide,” after the Sanskrit ananda, or bliss. It was left for animal physiologist Gary Weesner of the U.S. Department of Agriculture (USDA) to ask the burning question: “How do pigs use their anandamide?” In a study of the possibility of using anandamide as a safe sedative for animals, Dr. Weesner discovered that pigs treated with anandamide tended to show lower body temperature, slower respiration, and less movement — all indicators of a calmer porcine state of mind.

THC and its organic cousin make an impressive triple play in the brain: They effect movement through receptors in the basal ganglia, they alter sensory perception through receptors in the cerebral cortex, and they impact memory by means of receptors in the hippocampus. However, there has been little evidence in animal models for tolerance and withdrawal, the classic determinants of addiction. To the early researchers, it did not look like cannabis should be addictive. And for at least four decades, million of Americans have used marijuana without clear evidence of a withdrawal syndrome.

Nevertheless, some people appear to exhibit a classic pattern of dependency. By the year 2000, more than 100,000 Americans a year were seeking treatment for marijuana dependency, by some estimates. Marijuana Anonymous, an organization modeled on the principles of Alcoholics Anonymous, had become a robust recovery organization. What was going on?

Some of the mystery of marijuana’s effects was resolved after researchers demonstrated that marijuana definitely increased dopamine activity in the limbic area of the brain, as do all other addictive drugs. Tanda, Pontieri, and Di Chiara demonstrated that dopamine levels in the nucleus accumbens doubled when rats received an infusion of THC. It appears that marijuana also raises dopamine and serotonin levels through the intermediary activation of opiate and GABA receptors.

In 2004, a study group at the University of Vermont undertook a critical review of all major relevant studies of marijuana withdrawal. The meta-review appeared to bear out the theory that there are heavy marijuana users who suffer a verifiable and often vivid set of withdrawal symptoms when they try to quit. The most common clinically significant symptoms of abrupt withdrawal in heavy pot smokers, according to the research group, were

anxiety, decreased appetite/weight loss, irritability, restlessness, sleep problems, and strange dreams. These symptoms were associated with abstinence in at least 70% of the studies in which they were measured. Other clinically important symptoms such as anger/aggression, physical discomfort (usually stomach related) depressed mood, increased craving for marijuana, and increased sweating and shakiness occurred less consistently.

These are not trivial issues. As one long-time heavy cannabis user put it: “It’s not suicidal ideation but it’s the feeling that life will just never ‘be right’… when you suffer from symptoms that you’ve been told don’t exist, you are left looking for the wrong cause. So, if you’re told that marijuana withdrawal does not increase anxiety, anger, or ‘hopelessness,’ you want to look for a cause of those things… I went through withdrawal periods where I was inappropriately angry at the wrong thing, thinking that specific people were upsetting me when they were not.”

In the final post of this series, we will hear from more heavy marijuana users, in their own words. Personal observations and selected case histories of frequent marijuana users were gathered from anonymous, unedited comments posted on a blog site maintained by the author.

References

Hanson D. “Marijuana Withdrawal: A Survey of Symptoms.” In The Praeger International Collection on Addictions. Ed. by Angela Browne-Miller. Westport, Connecticut: Praeger, 2009. Vol. 2 pp.111-124.

Budney, A. (2004). Review of the Validity and Significance of Cannabis Withdrawal Syndrome American Journal of Psychiatry, 161 (11), 1967-1977 DOI: 10.1176/appi.ajp.161.11.1967

Kouri, E., & Pope, H. (2000). Abstinence symptoms during withdrawal from chronic marijuana use. Experimental and Clinical Psychopharmacology, 8 (4), 483-492 DOI: 10.1037/1064-1297.8.4.483

Rodriguez de Fonseca, F. (1997). Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal Science, 276 (5321), 2050-2054 DOI: 10.1126/science.276.5321.2050

Tanda, G. (1997). Cannabinoid and Heroin Activation of Mesolimbic Dopamine Transmission by a Common µ1 Opioid Receptor Mechanism Science, 276 (5321), 2048-2050 DOI: 10.1126/science.276.5321.2048

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The Many Facets of Addiction http://brainblogger.com/2009/04/25/the-many-facets-of-addiction/ http://brainblogger.com/2009/04/25/the-many-facets-of-addiction/#comments Sat, 25 Apr 2009 13:37:22 +0000 http://brainblogger.com/?p=2715 Neuroscience and Neurology CategoryThe science of neurology has created a paradigm shift in our basic understanding of the structure of the brain and the rest of the human nervous system. It has taken a long time, and a large group of doctors, clinicians and assorted scientists to piece together the ways in which this new knowledge of the brain has direct application to the states of mind and body we call addiction, alcoholism, or drug dependence.

When I first began following the subject of addiction in the early 1990s, the addiction field was still small, the insights highly tentative. However, what I had originally viewed as a series of potential breakthroughs in addiction research very rapidly became the tip of an enormous iceberg: brain science, and the revolutionary new directions represented by modern biology. The Chemical Carousel, my book on addiction research, is a snapshot in time of an extremely fast-moving landscape.

CandlelightHerewith, a few random samplings:

— As many as 30 percent of suicides every year may come from the nation’s pool of about 22 million alcoholics. Half of all emergency room patients with multiple fractures are alcoholics, according to research by prominent alcohol investigator George Vaillant. Female alcoholics develop liver diseases like cirrhosis more frequently than men do. 10 percent of the nation’s drinkers consume 50 percent of the alcohol purchased in America. Alcohol loses most its rewarding properties when brain receptors for opiates are blocked.

— Large numbers of addicted cigarette smokers suffer from clinical depression. Smoking a single cigarette has been likened by one nicotine researcher to “lighting a match in a gasoline factory.” Women who smoke more than 20 cigarettes a day face an 80 per cent greater risk of developing breast cancer, compared to non-smoking women. Roughly one out of every three women of childbearing age was a cigarette smoker in 1991. Former Surgeon General Everett Koop said tobacco smoking results in “a thousand funerals a day.”

— Large doses of methamphetamine can trigger psychotic episodes indistinguishable from schizophrenia. Vigabatrin, a drug for the treatment of epilepsy, may turn out to be the first government-approved treatment for meth addiction.

— Recent studies have documented the existence of severe caffeine addicts, who suffer significant depression and impaired cognition for several months following termination of coffee drinking.

— Mice that have been genetic altered so that they lack the ability to taste sweet foods still prefer sugar water to regular water. And PET scans of former bulimics (men suffer from it, too) disclosed that they showed a marked decrease in serotonin binding at 5HT receptors, compared to healthy, age-matched women.

— Between 3 and 7 percent of Americans are “poor metabolizers” due to a genetic variant for the enzyme CYP2D6. For them, the recommended drug dosage can be far too high.

— Notably, while there is little evidence in animal models for marijuana tolerance and dependence — the class determinants of addiction — a significant percentage of regular marijuana users report that they suffer from severe withdrawal symptoms when they abstain completely from pot. What has emerged in the past ten years is a profile of marijuana withdrawal, where none existed before. The syndrome is marked by irritability, restlessness, generalized anxiety, hostility, depression, difficulty sleeping, excessive sweating, loose stools, and loss of appetite. Many abstaining pot smokers complain of feeling like they have a low-grade flu, and they describe a psychological state of existential uncertainty — “inner unrest,” as one researcher calls it.

This is a finding I will pursue in the next post. I own and maintain the Addiction Inbox blog, and the amount of evidence posted there about marijuana withdrawal makes it a fascinating and controversial topic.

References

Hanson, Dirk. The Chemical Carousel: What Science Tells Us About Beating Addiction. North Charleston, SC: BookSurge Publishing, 2009.

The Chemical Carousel is an in-depth look at addiction science and medical treatments for drug dependence and alcoholism. An experienced science and business journalist, author Hanson brings a complex and widely misunderstood subject out of the shadows and into the light of understanding. In this groundbreaking and highly readable examination of addiction science and the biological, emotional, and scientific underpinnings of substance abuse, The Chemical Carousel breaks through the myths, while presenting the surprising and cutting-edge facts about addiction and its medical origins. Hanson leaves no stone unturned in this invaluable examination of why people become addicted.

— From the Publisher: Booksurge Publishing

Kreek, M., LaForge, K., & Butelman, E. (2002). Pharmacotherapy of addictions Nature Reviews Drug Discovery, 1 (9), 710-726 DOI: 10.1038/nrd897

Leshner, A. (1997). Addiction Is a Brain Disease, and It Matters Science, 278 (5335), 45-47 DOI: 10.1126/science.278.5335.45

Miller, William, and Kathleen, Carroll, Eds. Rethinking Substance Abuse:
What the Science Shows, and What We Should do About it
. New York: The Guilford Press, 2006.

National Center on Addiction and Substance Abuse at Columbia University. Women under the Influence. Baltimore: The Johns Hopkins University Press, 2006.

Vaillant, G. E., The Natural History of Alcoholism Revisited. Cambridge: Harvard University Press, 1995.

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