11/29/16

Marijuana & Adverse Health Effects

© David Castillo Dominici | 123rf.com

© David Castillo Dominici | 123rf.com

In the 2016 election there was another political milestone met besides the presidential election of Donald Trump—four more states voted to legalize recreational marijuana. California, Maine, Massachusetts, and Nevada joined Alaska, Colorado, Oregon, Washington and the District of Columbia. However, the public use of marijuana—recreational or medical—is still not permitted anywhere. Arkansas, Florida and North Dakota approved medical marijuana initiatives and Montana loosened restrictions on an existing medical marijuana law. The executive director of the Drug Policy Alliance was quoted in The Washington Post as saying: “The end of marijuana prohibition nationally, and even internationally, is fast approaching.”

Given the election of Donald Trump and the international position on marijuana, this may be more optimism than reality. Within the U.S. there has been clear momentum towards legalization of some kind, as there are now eight states and the District of Columbia where recreational marijuana is legal; and 28 states and the District of Columbia where medical marijuana is permitted. However, because of the ongoing federal classification of marijuana as a Schedule I drug, reliable research into the benefits and adverse health effects from marijuana use is hard to come by. The public needs to be more aware of the scientific research into the potential adverse effects and medical benefits from marijuana as the U.S. continues to move toward a complicated, patchwork quilt of varied state laws and regulations regarding marijuana.

A good place to start is with an article written by the current director of the National Institute on Drug Abuse (NIDA), Dr. Nora Volkow and three others, “Adverse Health Effects of Marijuana Use.” Volkow et al. reviewed the current state of the scientific findings on the adverse health effects related to the recreational use of marijuana. Their review focused on the areas where the evidence was the strongest. In a table summarizing their confidence in the evidence for adverse effects of marijuana on health and wellbeing, they gave the following assessment of marijuana use, particularly with heavy or long-term use that starts in adolescence.

Effect

Overall Level of Confidence

Addiction to marijuana or other substances

High

Diminished lifetime achievement

High

Motor vehicle accidents

High

Symptoms of chronic bronchitis

High

Abnormal brain development

Medium

Progressive use of other drugs

Medium

Schizophrenia

Medium

Depression or anxiety

Medium

Lung cancer

Low

Long-term marijuana use can lead to addiction; there’s no real doubt. About 9% of those who experiment with marijuana will develop dependence, according to the criteria for dependence in the DSM-IV. This increases to one in six (16.7%) among those who started using marijuana as teens. Daily smokers have a 25% to 50% risk of developing an addiction to marijuana. There is also a cannabis withdrawal syndrome, with symptoms such as: irritability, sleep difficulties, dysphoria (a state of being unhappy or unwell), cravings, and anxiety.

Since the brain remains in a state of active development until around the age of 21, individuals under 21 who use marijuana are more vulnerable to adverse long-term effects from marijuana use. Adults who smoked marijuana regularly during adolescence have impaired neural connectivity (fewer fibers) in certain brain regions.

The impairments in brain connectivity associated with exposure to marijuana in adolescence are consistent with … findings indicating that the cannabinoid system plays a prominent role in synapse formation during brain development.

While regular use of marijuana is associated with anxiety and depression, causality has not been established. Marijuana is also regularly linked to psychosis, especially among people with a predisposition. Heavy marijuana use, greater drug potency, and exposure at a young age can all negatively effect the experience of psychosis or schizophrenia, accelerating the time of a first psychotic episode by 2 to 6 years.

Because marijuana use impairs critical cognitive functions during acute intoxication and for days after use, many students may be functioning below their natural capabilities for long periods of time. “The evidence suggests that such use results in measurable and long-lasting cognitive impairments, particularly among those who started to use marijuana in early adolescence.” A failure to learn at school, even for short or sporadic periods of time because of acute intoxication, will interfere with the capacity to achieve educational goals. This seems to explain the association between marijuana use and poor grades.

Heavy marijuana use has been linked to lower income, greater need for socioeconomic assistance, unemployment’s, criminal behavior, and lower satisfaction with life.

There is also a relationship between THC levels in blood and performance in controlled driving-simulation studies. These studies have been a good predictor of real-world driving ability. “Recent marijuana smoking and blood THC levels of 2 to 5 mg per milliliter are associated with substantial driving impairment.” The overall risk of involvement in an accident increases by a factor of 2 when someone drives soon after using marijuana. Not surprisingly, combining marijuana and alcohol seems to result in greater risks than the use of either drug alone.

The authors noted that most of the long-term effects of marijuana use in the article have been seen among heavy or long-term users. Yet the presence of multiple confounding factors, including the frequent use of marijuana with other drugs, detracts from their ability to establish causality.

They also noted there is a need to improve our knowledge on the potential medical benefits of the marijuana plant. A report by the Institute of Medicine sees the benefits for stimulating appetite and in combating chemotherapy-induced nausea and vomiting, severe pain and decreasing intraocular pressure in the treatment of glaucoma. “Nevertheless, the report stresses the importance of focusing research efforts on the therapeutic potential of synthetic or pharmaceutically pure cannabinoids.” With all of its problems, the existing structure for the approval of new medicines through the FDA is better than the current lack of any safety and regulatory apparatus with medical marijuana. The ongoing failure to confirm or refute the plethora of health and medicinal claims with marijuana use is progressively taking us back to the days of patent medicine claims in state-by-state approval. In conclusion they summarized the results of their review of the literature on adverse effect from marijuana use as follows:

Marijuana, like other drugs of abuse, can result in addiction. During intoxication, marijuana can interfere with cognitive functions (e.g. memory and perception of time) and motor function (e.g. coordination), and these effects can have detrimental consequences (e.g. motor-vehicle accidents). Repeated marijuana use during adolescence may result in long-lasting changes in brain function that can jeopardize educational, professional, and social achievements. . . . . As policy shifts toward legalization of marijuana, it is reasonable and probably prudent to hypothesize that its use will increase and that, by extension, so will the number of persons for whom there will be negative health consequences.

A German review study by Hoch et al., “Risk Associated with the Non-Medical Use of Cannabis,” also sought to summarize the current state of knowledge regarding the physical and mental adverse effects of intensive recreational cannabis use. They came to conclusions similar to the Volkow et al. study. Hoch et al. noted the potential for addiction and withdrawal, mild negative effects on learning capacity, neurocognitive impairments with adolescents, an increased risk of psychosis, and others. “Further research is required to clarify the causal nature of the links between cannabis consumption patterns and adverse events.”

Empirical data have now clearly shown that starting early in life and regularly using high amounts of cannabis for a long period of time increases the risk of various mental and physical disorders and endangers age-appropriate development. Because many studies have failed to control properly for confounding variables, it still cannot be stated beyond doubt that there is a causal connection between cannabis consumption patterns and cognitive damage or the development of comorbid psychic or somatic disorders. The worldwide increase in the THC content of cannabis may increase the health risks, particularly for adolescent users. Further research is required to determine why some people are more affected than others by the unfavorable consequences.

On the other hand, another long-term study of chronic marijuana use among young adult men by Bechtold et al., was published  in the journal, Psychology of Addictive Behavior. The study used data from The Pittsburgh Youth Study, a longitudinal study that followed seventh grade students until they were 36. The study found that chronic marijuana users were no more likely than other groups to experience several physical or mental health problems, including early onset psychosis and heart problems. Some limitations in applying the findings of this study would include the fact that participants were only followed until the age of 36, perhaps too early for many of the health problems to become evident. Another difference was that the heaviest use category for marijuana was “more than 3 times per week,” while Volkow et al. seems to have been looking at daily or almost daily use.

In a postscript addition to the above studies, a 2016 study by Columbia researchers found evidence of a compromised dopamine system in heavy marijuana users. Dopamine levels were lower in the striatum, an area in the brain involved in working memory, impulsive behavior and attention. Previous studies have found addiction to other drugs of abuse, like cocaine and heroin, have similar effects on dopamine release. This was the first such evidence for marijuana.

A press release by the Columbia University Medical Center quoted the lead author as stating that in light of the increasing use and acceptance of marijuana, especially by young people, it is important to look more closely at the potentially addictive effects of cannabis on key regions of the brain. The study was small, with 11 adults who were severely dependent upon marijuana and 12 matched healthy controls. The average age of onset among the marijuana users was 16, with dependence occurring by 20. In the month before the study, all users in the study had smoked daily.

“Compared with controls, the cannabis users had significantly lower dopamine release in the striatum, including subregions involved in associative and sensorimotor learning.” The investigators also explored the relationship between dopamine release in the striatum and cognitive performance on learning and working memory tasks. The bottom line was that long-term, heavy marijuana use could impair the dopaminergic system, which in turn could have a series of negative effects on learning and behavior.

I talked with someone who had been to California a few weeks after the 2016 election when recreational marijuana use was legalized. She reported how employees of her hotel were gathering outside on their break to smoke pot, similar to what cigarette smokers do. If legal recreational use becomes more widespread in the U.S., the adverse physical and mental adverse effects from heavy, regular use will also become more evident. Then marijuana use will take a place beside alcohol use and tobacco use as a public health problem.

11/25/16

Structure of an Evolutionary Revolution

Editorial cartoon of Darwin as an ape (1871)

Editorial cartoon of Darwin as an ape (1871)

In the mid 1990s I had the opportunity to attend a local community play in the Rhea County Courthouse located in Dayton Tennessee. This courthouse was where one of the most famous trials of the twentieth century took place, the Scopes Trial. The New York Times described what took place there as “one of the most colorful and briefly riveting of the trials of the century that seemed to be especially abundant in the sensation-loving 1920s.” Every July local residents put on the play in the second floor courtroom, which has been restored to look the way it did during the July 1925 trial. In front of the courthouse is a plaque commemorating the place where John Scopes was convicted of violating a state law by teaching that humans descended from a lower order of animals.

In the basement of the courthouse is a museum, which contains memorabilia like the actual microphone used to broadcast the trial. When the annual play is put on, some of the museum pieces are used as props in the trial. The play’s dialogue is taken primarily from the transcript of the trial itself. The audience sits in chairs facing the judge’s bench. Members of the audience are selected to portray the jury, whose only task was to sit in the jury box and then leave the courtroom several times during the play when the real jury was excused.

Scopes was found guilty and he was fined $100, the minimum penalty. His attorney appealed the case to the Tennessee Supreme Court, which threw out his conviction on a technicality. He went on to study geology at the University of Chicago (on a scholarship by his supporters) and became a petroleum engineer. But almost 100 years later, his trial still represents one of the seminal times in American history where there was a clash between science and religion. Clarence Darrow, the famous defense lawyer who was one of the lawyers on the defense team for Scopes, said in his closing remarks:

 I think this case will be remembered because it is the first case of this sort since we stopped trying people in America for witchcraft . . . We have done our best to turn the tide . . . of testing every fact in science by a religious doctrine.

That sentiment is still alive today, as is the perceived conflict between the scientific theory of evolution and the religious doctrine of creation. The public portrayal of the so-called evolution-creation “debate” has misconceptions similar to those evident in Darrow’s statement. One example of thie misconception is an article Rachael Gross wrote for Slate a couple of years ago, celebrating how “Evolution is Finally Winning Out Over Creationism.” A key factor in her analysis was pointing to how “a majority of young people endorse the scientific explanation of how humans evolved.” By scientific she means a purely secular evolution—something not directed by any divine power.

Her hope is there will be a continual shrinkage of those who oppose evolution. One way this would occur is through individuals “converting” to evolution, regardless of their political and religious beliefs. “For the movement behind evolution to triumph, younger Americans who have been raised to believe in creationism need to be open to changing their minds.” Another way is by “generational momentum,” meaning that the switch will happen as older adults who believe in creationism die off. This is not really simply a crass hope based on waiting for old people to die or that young people will switch their views with regard to the “doctrine” of evolution.

It also reflects the thought of science philosopher Thomas Kuhn in his book, The Structure of Scientific Revolutions. In this seminal work on the history and philosophy of science, Kuhn said that normal science referred to research firmly based on one or more past scientific achievements that a particular scientific community “acknowledges for a time as supplying the foundation for its further practice.” The process of normal science takes place within a scientific paradigm—where research occurs within the context of a scientific community committed to the same rules and standards for scientific practice. “That commitment and the apparent consensus it produces are prerequisites for normal science.” Kuhn acknowledged that the notion of his term ‘paradigm’ is intrinsically circular: “A paradigm is what the members of a scientific community share, and, conversely, a scientific community consists of men [and women] who share a paradigm.”

Any new interpretation of nature, whether a discovery or a theory, emerges first in the mind of one or a few individuals. It is they who first learn to see science and the world differently, and their ability to make the transition is facilitated by two circumstances that are not common to most other members of their profession. Invariably, their attention has been intensely concentrated upon the crisis-provoking problems; usually, in addition, they are men [or women] so young or so new to the crisis-ridden field that practice has committed them less deeply than most of their contemporaries to the world view and rules determined by the old paradigm. How are they able, what must they do, to convert the entire profession or the relevant professional subgroup to their way of seeing science and the world? What causes the group to abandon one tradition of normal research in favor of another?

In answering these questions, Kuhn went on to observe that the proponents of competing paradigm are always at least slightly at cross-purposes. “Neither side will grant all the non-empirical assumptions that the other needs in order to make its case.” While each may hope to “convert” the other to his or her way of seeing science and its problems, the dispute is not one “that can be resolved by proofs.” Kuhn quoted the theoretical physicist Max Planck who said: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.” Kuhn went on to say:

The transfer of allegiance from paradigm to paradigm is more like a conversion experience that cannot be forced. Lifelong resistance, particularly from those whose productive careers have committed them to an older tradition of normal science, is not a violation of scientific standards but an index to the nature of scientific research itself.

Darwin’s theory now exists as a foundational paradigm for a secular understanding of human origins. Within this context, Rachael Gross hopes for a completed paradigm shift within evolution that denies the possibility of any intervention from outside of the natural order. Young adult believers in creation need to convert fully to a belief in secular evolution. There is no room in her sense of evolution for theistic evolution/evolutionary creation. At most, it exists as a way station on the journey to secular evolution.

From this perspective, evolutionary creation unscientifically combines religious belief and evolution. Its needs to be jettisoned within a sincere scientific conversion experience to evolutionary belief. Older adults who are committed to the unscientific tradition of creation need to die off. Gross is carrying the banner once waved by Clarence Darrow in the Scopes Trial: “We have done our best to turn the tide . . . of testing every fact in science by a religious doctrine.” The evolutionary revolution marches on.

Darrow and Bryan

Darrow and Bryan

However, there is an unacknowledged assumption with regard to the philosophy of science when Gross equates secular evolution with “science.” Basic philosophical assumptions necessary for science include that nature is uniform; and that observable patterns in nature provide clues to help us understand the unobservable patterns and processes in nature. Our knowledge of the processes and patterns in nature is limited since we have not yet examined all there is to see in nature, nor have we observed it throughout it entire existence. This uniformity in nature is then necessarily assumed to hold universally. We assume the uniformity of natural causes in creation, in nature, but cannot prove it is true scientifically.

Francis Schaeffer pointed out that while early scientists like Francis Bacon and Isaac Newton believed in the uniformity of natural causes, they did not believe this natural uniformity existed in a closed system. He said this little phrase constituted the difference between natural science and a science rooted in naturalistic philosophy. It was the difference between what he called modern science and modern, modern science. In Escape from Reason, Schaeffer said: “It is important to notice that this is not a failing of science as science; rather the uniformity of natural causes in a closed system has become the dominant philosophy among scientists.”

Secular evolution would then be the product of what Schaeffer called modern, modern science. It rejects the possibility of a god or transcendent power outside of nature utilizing the natural process of evolution to develop life on earth. From this perspective, the Scopes Trial was fundamentally a dispute over two different systems of scientific philosophy with regard to evolution. The ridicule of literalist biblical belief and interpretation, embodied in the exchange between Darrow and Bryan, was collateral damage in the exchange. The underlying structure of the dispute over evolution is over the philosophical basis on which science can be done.

Pitting religion and science against one another as Darrow, Bryan and others have done, not only sets up a false dichotomy between them, it gives a distorted view of what the evolution revolution is all about.

If you are interested in learning more about the Scopes Trial, try this page about the Scopes Trial Museum or the Wikipedia page on the Scopes Trial. You can also read: Summer for the Gods, a Pulitzer Prize winning book about the Scopes Trial and “No Contest; No Victory.” Also, look at: When All the God Trembled, which discusses Darwinism and the Scopes Trial.

11/22/16

Antidepressant Misuse Disorder

54164089 - antidepressant pills 3d rendering isolated on white background

© Olekii Mach | 123rf.com

Chances are you know someone who is using an antidepressant. But that doesn’t necessarily mean the person you know has a problem with depression. In 2015, Takayanagi et al. published a study in The Journal of Clinical Psychiatry found that: “Among antidepressant users, 69% never met criteria for major depressive disorder (MDD); and 38% never met criteria for MDD, obsessive-compulsive disorder, panic disorder, social phobia, or generalized anxiety disorder in their lifetime.” Their data indicate that antidepressants were commonly used in the absence of “clear evidence-based indications.”

Writing for Mad in America, Justin Karter noted that previous studies revealed antidepressants were being over-prescribed and prescribed off-label. But others countered that these studies underestimated the lifetime prevalence of so-called mental disorders. The Takayanagi et al. study sought to address this criticism by conducting in-depth interviews to estimate whether participants met criteria for “mental disorders” over their lifetime. The study also indicated an individual was more likely to be prescribed an antidepressant if they were a woman, white, reported physical pain or discomfort to their doctor, or had recently visited a mental health care facility.

Another 2015 report by Kanton et al. published in JAMA found that the percentage of Americans on antidepressants increased from 6.8% to 14% between 1999 and 2012. The report’s authors speculated that the increase could in part reflect shifting attitudes regarding depression. Commenting on this report, Justin Karter pointed out how the increase likely includes a large proportion of off-label use of antidepressants. As was noted above, 69% of antidepressant users did not meet the criteria for major depression.

A JAMA study published in May of 2016 by Wong et al. found that 45% of the prescriptions given for antidepressants were to treat anxiety disorders, pain, insomnia and various other conditions. The study, which was done in Quebec Canada, looked at all adult prescriptions written for antidepressants (100,000 patients) between January 1, 2006 and September 30, 2015. Prescriptions for monoamine oxidase inhibitors were excluded. Prescriptions were classified as on or off label depending upon whether the drug was approved by Health Care of Canada or the FDA for the indication noted by September 0f 2015. Physicians prescribed antidepressant off-label for anxiety disorders (18.5%), insomnia (10.2%), pain (6.1%) and panic disorders (4.1%).

An online survey of long-term antidepressant patients by Cartwright et al., published in Patient Preference and Adherence, found that almost 90% reported some degree of improvement, with 30% also saying they had moderate to severe bouts of depression during treatment.  Ten different adverse effects were reported by over 50% of the participants. The five most common were: withdrawal effects (73.5%), sexual dysfunction (71.8%), weight gain (65.3%), feeling emotionally numb (64.5%), and failure to reach orgasm (64.5%). “Between 36% and 57% of respondents experienced these adverse affects at either a moderate or severe level.” Additional adverse effects reported included: agitation (55.1%), feeling not like myself (54.4%), reduced positive feelings (45.6%), caring less about others (36.4%), suicidality (36.0%), and feeling aggressive (31.6%).

Some patients in this study were particularly concerned about severe withdrawal symptoms that undermined their confidence to discontinue should they wish to and therefore limited their choices. In line with this, 45% patients also believed that they had some level of addiction to the antidepressant. Some patients were also critical of the lack of information given by prescribers with regard to adverse effects, including withdrawal symptoms. Some also expressed disappointment or frustration with the perceived lack of support available to them in managing withdrawal.

Limitations of the study include the fact that the data were self-reported and that the study was not a randomized control study—the gold standard methodology for evidence-based medicine. However, there are relatively few long-term outcome studies of antidepressant use.

A 2009 systematic review published in the Journal of Affective Disorders, concluded that long-term outcomes in depression were poor, with no clear relationship between drug treatment and positive outcomes.  The outcomes for non-antidepressant treatment were no worse than those for antidepressant treatment.

Overall 40% to 85% of patients experienced a recurrence during follow-up. Average time to recurrence was around 3.2 years across eight studies that provided data on this outcome. Around 25% of patients achieved a global rating of well or improved at the end of the study and a similar number had a poor outcome marked by multiple recurrences or continuous impairment. Most participants recovered from the index episode, but experienced multiple recurrences.

The August 2016 issue of Psychotherapy and Psychosomatics published a literature review of long-term use of newer generation antidepressants (i.e., SSRIs and SNRIs and others) by Carvalho et al. While many side effects were transient, disappearing after a few weeks, other potentially serious adverse events may persist or occur later. The main adverse events related to using newer antidepressant drugs included the following:

  • Gastrointestinal issues
  • Weight gain and metabolic disturbances
  • Genitourinary issues (issues related to the genital or urinary organs)
  • Sexual dysfunction
  • Hyponatremia (low sodium level in the blood)
  • Osteoporosis and risk of fractures
  • Bleeding
  • Central nervous system issues
  • Sweating
  • Sleep disturbances
  • Affective disturbances
  • Suicidality
  • Discontinuation syndromes

You can read more information on the above adverse effects and others in the Carvalho et al. review. What follows is a brief discussion of their findings for weight gain and diabetes, bleeding, sleep disturbances, affective disturbances, suicidality, and discontinuation syndromes.

Several studies have shown that long-term use of antidepressants (more than 6 months) is associated with weight gain. Paroxetine (Paxil) may be the worst offender. A population-based study indicated the use of antidepressants could be associated with a higher risk of obesity. The association between antidepressants and diabetes mellitus is inconclusive. Some reports indicate a higher risk; others do not. But a recent review and meta-analysis found that SSRIs were associated with an increased risk of diabetes mellitus.

All SSRIs have been associated with an increased risk of bleeding. “The most likely mechanism responsible for these adverse reactions is a reduction of serotonin reuptake by platelets.” Fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) have a higher risk of platelet dysfunction than other SSRIs. Veniafaxine (Effexor) and mirtazapine (Remeron) have been associated with an increased risk of bleeding. SSRIs have been associated with a higher risk of bleeding during operations.

Sleep disturbances are one of the hallmark symptoms of depression. However,  studies have shown that SSRIs and Effexor are associated with increased REM sleep latency and an overall reduction in the time spent in REM sleep. These effects are usually associated with the initial period of treatment and may return to baseline after 8 weeks. Remeron and trazodone have been associated with improving sleep. In my clinical experience, trazadone is regularly used off-label to help promote sleep.

Many individuals taking SSRIs report they experience emotional blunting. They say their emotions have been “toned down.” Others say they just don’t care about issues that were significant to them before. “Evidence indicates that these adverse affective manifestations may persist even after the symptoms of depression have improved and can occur in patients of all ages.” Mania or agitation can occur. These response have been said to unveil unrecognized bipolar disorder. But since this can also occur in previously unipolar patients, the mania could be drug-induced. An activation syndrome, where patients experience anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness and impulsivity can occur.

Carvalho et al. limited the occurrence of these adverse effects to the first three months of treatment. However, psychiatrist Peter Breggin has documented the emergence of agitation and activation with antidepressants in Medication Madness and other writings. Carvalho et al. said using antidepressants could also be associated with the return of depressive symptoms during baseline treatment, and the appearance of new symptoms or paradoxically, exacerbate the baseline clinical picture. The occurrence of paradoxical effects was reported in random control trials with Prozac and Zoloft.

The emergence of suicidality and self-injurious behavior with antidepressant treatment is one of the most debated and controversial risks. Nevertheless, the FDA has required a black box warning regarding the risk of suicidality for children and adolescents using antidepressants since 2014. The incidence of successful and attempted suicide has been frequently underreported in antidepressant RCTs. Carvalho et al. said:

Two recent meta-analyses have not identified a clear increased risk of treatment-emergent suicidality in adult individuals treated with antidepressants in RCTs. Notwithstanding that the use of antidepressants is efficacious for the treatment of MDD in adults, there is no clear evidence for either specific protective effects or increased risk related to suicidality.

Often underappreciated, is the emergence of withdrawal symptoms of varying degrees with treatment discontinuation and/or interruption with almost all SSRIs and SNRIs. These reactions have been described as “discontinuation syndromes” in an attempt to avoid the suggestion of dependence that could effect marketing. A review suggested the dependence and withdrawal with newer antidepressants was comparable to those experienced with benzodiazepines. “Due to the severity and unpredictability of these manifestations, it has been recently suggested that the term ‘discontinuation syndrome’ should be replaced by ‘withdrawal syndrome.’” These symptoms can include:

flu-like symptoms, tremors, tachycardia, shock-like sensations, paresthesia, myalgia, tinnitus, neuralgia, ataxia, vertigo, sexual dysfunction, sleep disturbances, vivid dreams, nausea vomiting, diarrhea, worsening anxiety and mood instability.

In their conclusion, Carvalho et al. said the common belief of fewer side effects with the newer generation antidepressants (especially the SSRIs) only pertains to their safety in overdose. “On the contrary, the long-term use of SSRIs and SNRIs is likely to yield important side effects.” The likelihood of treatment-emergent adverse effects is related to the duration of antidepressant treatment—particularly with weight gain, diabetes, and osteoporsis. Some adverse side effects may persist long after discontinuation of the drug. Particularly following long-term use, antidepressants,

 … may increase the risk of experiencing additional psychopathological (e.g. treatment emergent affective switches and paradoxical symptoms), or medical (e.g. obesity and bleeding) problems that do not necessarily subside after discontinuation of the drug.

This leads to their conclusion that: “The findings of this review suggest that long-term treatment with new generation ADs should be avoided if alternative treatments are available.”

11/18/16

National ADHD Epidemic

© kentoh | stockfresh.com

© kentoh | stockfresh.com

The CDC published a study that found 11% of school-aged children in the U.S. between 2003 and 2011 had received an ADHD diagnosis. This statistic meant that 6.4 million children, 1 in 5 boys and 1 in 11 girls, were said to have ADHD. A different CDC report indicated the American Psychiatric Association (APA) estimated in their 2013 edition of the DSM, the DSM-5, that only 5% of children have ADHD. The rates of ADHD diagnosis are increasing over time, from an average of 3% per year between 1997 and 2006, to 5% between 2003 and 2011. The prevalence of children between the ages of 4 and 17 diagnosed with ADHD varied widely by state. In 2011, the lowest reported rates were in Nevada (5.6%); the highest rates were in Kentucky (18.7%). In contrast, the percentage of children diagnosed and medicated for ADHD in France is less than half of one percent—.5%!

You can see the CDC reports cited above here, here and here.

Writing for Psychology Today in 2012, Marilyn Wedge noted in “Why French Kids Don’t Have ADHD,” how the difference seemed to turn on how ADHD was conceived. In the U.S. ADHD is seen as a biological disorder with biological causes. So the go-to treatment method is stimulant medications. Dr. Wedge also pointed that French psychiatrists did not use the DSM system to diagnose childhood emotional problems. Instead they used an alternative classification system that focuses on the underlying psychosocial causes of a child’s symptoms.

French child psychiatrists, on the other hand, view ADHD as a medical condition that has psycho-social and situational causes. Instead of treating a child’s focusing and behavioral problems with drugs, French doctors prefer to look for the underlying issue that is causing the child distress—not in the child’s brain but in the child’s social context. They then choose to treat the underlying social context problem with psychotherapy or family counseling. This is a very different way of seeing things from the American tendency to attribute all symptoms to a biological dysfunction such as a chemical imbalance in the child’s brain.

She commented that the holistic, psychosocial approach of the French allowed for the possibility there could be nutritional factors that worsen ADHD symptoms. “In the U.S., the strict focus on pharmaceutical treatment of ADHD, however, encourages clinicians to ignore the influence of dietary factors on children’s behavior.”

Psychiatrist Robert Berezin commented on Wedge’s report saying that it seemed American boys had contracted some contagion that spread ADHD exponentially. More seriously, he went right to the heart of the problem: if ADHD rates are so drastically different between the U.S. and France, how can ADHD be a brain disease? “Yes there can be symptoms of hyperactivity and concentration. But it is created by psychosocial causes, not biological ones. And the treatments should be appropriate to the cause.” He concluded that the French situation showed that so-called ADHD was a psychosocial problem, not a brain disease.

So if we accept this conclusion, where does this leave us in America with regard to ADHD and the aftermath of decades of conceiving and treating it as a brain disease? A recent investigative report by the Milwaukee Journal Sentinel and MedPage Today pointed out several areas of concern. First is the increase in the diagnosis of Adult ADHD. Twenty years ago ADHD was rarely diagnosed in adult Americans. Now, 1 in 23 adult Americans, around 10 million people, are said to have ADHD. And there has been a fourfold increase among adults 26 and older who use Adderall recreationally.

The reporters cited a 2010 study where 22% of the adults tested for ADHD had exaggerated their symptoms. This finding underscores how college-aged adults increasingly use ADHD medications as  “study aides.” A 2013 study found wastewater samples collected near college dormitories in Tacoma Washington were eight times higher for amphetamines during final exams week than during the first week of classes. Although FDA adverse events indicated there were more reports for children, the adults were reporting more serious adverse events. “Adults accounted for just over one-third of reports, but made up more than half of all hospitalizations and 85% of deaths.”

Experts question whether adult ADHD is truly a widespread condition that needs treatment with the array of FDA-approved prescription medications. A medical historian, Nicolas Rasmussen, was quoted as saying that amphetamines are grossly overused; and that “the streets are awash with Adderall.”

Drug companies counter that ADHD is a real and treatable medical condition that effects millions of Americans. Charles Catalano, a spokesperson for Shire, which manufactures two ADHD medications, Vyvanse and Adderall, said the drugs have been approved by regulators around the world and are safe to use. “Our medications are proven to be effective when used according to prescribing practices of a licensed, trained health care professional.” A spokesperson for Novartis, the manufacturer of Ritalin, said it has been used safely and effectively for more than 60 years. “If used inappropriately, the results could be serious, just like with the misuse of any other medication.”

The DSM-5, published in 2013 by the APA, relaxed the criteria for diagnosing adult ADHD. Previously adults needed to have six of nine possible symptoms. Now they only need five of nine symptoms. Seventy-eight percent of the panel of experts who approved the changes had financial ties to drug companies. The APA minimized the potential conflicts of interest by stating no panel member had made more than $10,000 a year working as industry speakers and consultants.

Moffitt et al. published the results of a forty-year study of individuals in New Zealand in The American Journal of Psychiatry. The study found that found 90% of adult ADHD cases did not have a history of childhood ADHD. “The findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder.” The authors added that if the findings were replicated, adult ADHD’s place in the DSM should be reconsidered and that research needs to investigate the etiology of adult ADHD.

It also appears that using ADHD medication leads to addiction and abuse problems with some individuals. Some of this is simple common sense. All ADHD stimulant medications are Schedule II controlled substances, meaning that the DEA considers them to have the same addictive potential as cocaine. Yet the research literature presents conflicting accounts. Some studies report that untreated ADHD is a significant risk factor in developing substance use disorders. Others suggest there is no compelling evidence that treating children with ADHD medication leads to an increased risk of later substance use problems.

A Medscape article concluded that the bulk of evidence suggested that treating ADHD with stimulant medication did not increase the risk for developing a substance use disorder, nor did it decrease to risk. At the very end of the article this comment appeared: “This activity is supported by an independent educational grant from Shire.” The author of the article had also received grants and served as a paid consultant for Shire.

On the other hand, Peter Breggin and others have noted there is a high abuse liability with stimulant medications. A 1995 DEA report indicated there was an abundance of scientific literature on the abuse potential of Ritalin and other Schedule II stimulants. A 1998 NIH conference on the “Diagnosis and Treatment of ADHD” stated: “An extensive scientific literature spanning more than 30 years of research unequivocally indicates that MPH [Ritalin] has a high abuse liability.” A 1995 study by Nora Volkow and others found that cocaine and MPH had similar effects on the brain when given intravenously. Breggin commented in his discussion of the study in his book, The Ritalin Fact Book, that the main difference was the longer lasting effect of Ritalin. This was speculated to be why Ritalin was less subject to abuse than cocaine. Breggin said:

What does all of this mean in plain English? Ritalin’s biochemical mechanism of action is essentially the same as that of cocaine, and therefore Ritalin produces similar effects to cocaine. In fact, all of the stimulants, including Ritalin and cocaine, jack up dopamine, serotonin, and norepinephrine chemical messengers in the brain, producing a variety of similar mental abnormalities. If given intravenously, the “high” is the same for all of them.

A study by Schrantee et al. published in the September issue of JAMA Psychiatry found there was a distinct effect of methylphenidate (Ritalin) on the brains of children and young adults. A discussion of this study in an article on Mad in America indicated the lead researcher of the study’s team, Liesbeth Reneman, said given that maturation of several brain regions are not complete until adolescence, drugs given during the sensitive, early phases of life could effect “neurodevelopmental trajectories” and have profound effects later in life.

The adolescent brain is a rapidly developing system that maintains high levels of plasticity. As such, the brain may be particularly vulnerable to drugs that interfere with these processes or modify the specific transmitter systems involved.

The mesolimbic dopamine system (MDS), the reward pathway of the brain, is one of those later maturing brain regions. Incidentally, the MDS is probably the region of the brain where drugs produce dependence. In his book, The Science of Addiction, Carleton Erickson said neuroscientists believe that when the functioning of certain MDS neurotransmitter systems are disrupted from genetic “miswiring” and/or long-term exposure to a drug, “chemical dependence as a bran disease” can develop.

The Schrantee et al. study is the first evidence that using ADHD medications can alter brain development. So studies of the long-term consequences need to be completed. But one of the questions that should be investigated is does the long-term use of stimulant medications effect changes to the MDS of the brains of adolescents and young adults and are those changes related to a greater risk of substance abuse. Hopefully we’ll have some answers before prescription stimulant drugs compete with opioids as a national drug epidemic.

11/15/16

Genealogies in Genesis

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© sylverarts | 123rf.com

One of the fundamental issues in the dispute over a Biblical understanding of the age of the earth is how the genealogies in Genesis should be interpreted. Bishop Ussher’s chronology dated the creation of the heavens and earth in Genesis 1:1 to a very specific date in 4004 BCE. Editions of the King James translation of the Bible (KJV) began to disseminate his chronology in the 1650s. Then beginning in 1701, William Lloyd’s annotated edition of the KJV included Ussher’s chronology within marginal annotations and cross-references. The popular Scofield Reference Bible (1909/1917) also used it, which helped establish Ussher’s chronology as one of the key theological pillars of modern young earth creation belief.

Intriguingly, Ussher appears to have done his work in the midst of a dispute over biblical chronology in his time. According to The Oxford Handbook of the Bible in Modern England, c. 1530-1700, Robert Carey believed that errors in standard accounts of biblical history, relying on the apparent chronology of the Hebrew text, had provided the opportunity for some to attack the integrity and truth of the Bible. “He was critical of those who wanted to use apparent technical problems in biblical chronology to cast doubt on doctrinal certainties.” Cary and others believed that using the records of alternative sources could help resolve some of the apparent discrepancies. This was later referred to as scientific chronology, using the records of ancient history to make sense of the Bible.

Ussher’s conclusions seemed to bring a greater degree of certainty to a biblical chronology derived from the Hebrew Bible and orthodox readings of the text. His writings did this “at a time when chronology had become one of the most important determinants in a serious debate about the transmission and authority of the text of the Old Testament.” He was one of the first individuals to be fully aware of the variety of manuscript witnesses for biblical history “and the discrepancies in ancient testimony regarding the Old Testament.” His solution was to affirm the authority of the Hebrew Bible by his own extensive inquiries into the preservation and transmission of alternative textual witnesses, such as the Samaritan Pentateuch and the Septuagint.

So Ussher’s affirmation of the creation of the world at nightfall on Saturday, October 22, 4004 BCE, occurred within the context of disputes over the apparent chronology of the Hebrew text. At that time, certain individuals used these discrepancies to cast doubt on the transmission and authority of the text of the Old Testament. Today, holding to Ussher’s chronology is still seen as an integral part of affirming the authority of Scripture for many who hold to a young earth creation viewpoint.

Writing for the Institute for Creation Research, John Morris noted the association of Ussher’s chronology with the KJV in “Can the Ussher Chronology Be Trusted?” Morris clearly accepts Ussher’s dating for “all important historical events, beginning at creation and extending to the destruction of Jerusalem in a.d. 70.” He noted where an ICR colleague had modernized the language of Ussher’s original work, and hoped it would re-establish Ussher’s chronology as a standard research tool and restore for some, “their confidence in the Biblical record.”

In another ICR article, James Johnson used ‘simple math’ and the data provided in Genesis to conclude there was no good excuse for doubting the biblical chronological data. He rejected the “irrelevant” issue of whether Genesis genealogies were open (whether they skip generations and have gaps) or closed (the genealogies are complete). Upon completion of his own interpretation of Genesis timeframes, he said there was no good excuse for doubting the biblical chronological data as he presented it.

Yet biblical scholars beginning with William Henry Green in 1890 have continued to raise questions regarding the validity of Ussher’s chronology. Green’s article, “Primeval Chronology,” was published in the journal, Bibliotheca Sacra. He said the biblical genealogies in Genesis 5 and 11 were not intended for the construction of chronology.

It can scarcely be necessary to adduce proof to one who has even a superficial acquaintance with the genealogies of the Bible, that they are frequently abbreviated by the omission of unimportant names. In fact, abridgment is the general rule, induced by the indisposition of the sacred writers to encumber their pages with more names than were necessary for their immediate purpose. This is so constantly the case, and the reason for it so obvious, that the occurrence of it need create no surprise anywhere, and we are at liberty to suppose it whenever anything in the circumstances of the case favors that belief.

Several modern evangelical Old Testament scholars concur with Green. C. John Collins, as he discussed the biblical evidence for a historical Adam and Eve in Did Adam and Eve Really Exist?, noted that the genealogies in Genesis 4-5 do not claim to name every person in the line of descent from Adam, and therefore aren’t aimed at “providing detailed chronological information.” He added there was no way he knew of to assess what size gaps these genealogies allow. “It does not appear that they are intended to tell us what kind of time period they are describing.”

In his Genesis commentary from The Story of God Bible Commentary series, Tremper Longman said not all the genealogies in Genesis are of the same type or purpose. They are “ancient Near Eastern, not modern Western, genealogies.” The two main kinds of genealogies found in the Bible are linear and segmented. Linear genealogies go from father to one son (or ancestor), while segmented ones name a number of sons (or ancestors) from one father, as in Genesis 10. “Ancient genealogies are fluid.” They can skip generations. “They can change in order to reflect contemporary social and political realities.” According to R. R. Wilson, they are not normally created for historical purposes or intended to be historical records.

In the Bible, as well as in the ancient Near Eastern literature and in the anthropological material, genealogies seem to have been created for domestic, political-jural, and religious purposes, and historical information is preserved in the genealogies only incidentally.

The Eerdmans Bible Dictionary had a similar view on genealogies. It too said linear and segmented were the two major types of biblical genealogies. “Both types show fluidity among the middle names; names may be omitted or rearranged, or relationships changed.”

The Hebrews, like other ancient Near Eastern peoples, used genealogies to authenticate rights of inheritance (Num. 27:1–11), enhance the social position of outsiders (e.g., Caleb, son of Jephunneh the Kenizzite [Num. 32:12; Josh. 14:6; 15:13], becomes a son of Hezron—part of Judah; 1 Chr. 2:18), establish royal and cultic lineages (e.g., David, 1 Chr. 3; priests, 2 Chr. 31:16–19; Levites, Neh. 7:43–45; temple servants, vv. 46–56), and organize their social geography (Gen. 10). Usually only men are recorded.

Genesis 10 provides a list of the descendants of Noah. Many of the names in what is called the “Table of the Nations” have been identified with racial, geographical and political entities outside of the Bible. The following map, based on the Table of the Nations in Genesis 10, was taken from the New Bible Atlas:

nationsIn his Genesis commentary, Bruce Waltke said genealogies serve several purposes in Genesis—purposes which depend in part upon the nature of the genealogy itself. Broad genealogies present only the first generations of descendants (the sons of Leah or the sons of Rachel in Genesis 35:23-26). Deep genealogies list sequential descendants, usually from two to ten. Linear genealogies display only depth (Genesis 4:17-18). Segmented genealogies display both depth and breadth (Genesis 10:1-29; cf. 11:27-29; 19:36-38). “The distinctions of broad, deep, linear and segmented genealogies help explain the various functions of genealogies.”

By tracing their lineage back to a common ancestor, broad and segmented genealogies show the existing relationships between kinship groups. Genealogies were used in tribal societies to express the rights and privileges within social relationships, rather than strict biological kinship. The Table of Nations noted above expressed the kinship and distinctions between Israel and the surrounding nations. “The segmented lists of tribes in Gen. 46:8-25 display both the unity of all Israel and the distinctness of its tribes.”

However the linear genealogies in Genesis 4:17-18, 5:1-31; 11:10-26 are used to establish continuity over time without narrative. “Because the genealogies are concerned to propel the story and establish relational links, they cannot be used to compute absolute chronology.” For example, although the pre-flood genealogy of 5:1-31 and the post-flood genealogy of 11:10-26 record the ages when an individual fathered a son and then died, they don’t give the complete sum of time for the life spans of the individuals. If the narrator intended to establish an absolute, or “closed” chronology, this is a surprising omission.

Comparing shorter and longer genealogies that cover the same time periods elsewhere in the Bible suggest the shorter ones contain gaps. We see this in Exodus 6:14-25 with four generations from Levi to Moses, while 1 Chronicles 7:23-27 gives ten. Similar to the division of history into three periods of fourteen generations in the first chapter of Matthew, the division of history between Adam and Abraham into two equal divisions of ten generations (5:1-32 and 10:10-26) seems “artistic.”

Linear genealogies also demonstrate the legitimacy of an individual in his office; or give a person of rank connections to a worthy family or individual of the past. “This purpose was unaffected by the omission of names.”  We see this in Genesis 5, which showed that Noah was the legitimate descendant of Adam through Seth. “By beginning Noah’s ancestry with Adam, whom God created in his image, this genealogy represents Noah and his ancestry as the worthy bearers of the divine image mandated to rule the earth.”

By linking the genealogies by tôleō [generations] and connecting the twelve tribes of Israel to Noah’s son, Shem, the narrator demonstrates the legitimacy of the twelve tribes of Israel as image bearers, destined to subdue the earth, and as the worthy seed of the woman that will vanquish the Serpent. From those tribes Judah emerges as leader at the end of Genesis. His eternal son will rule forever over the nations (Gen. 49:8-12).

With all due respect to Bishop Ussher, his chronology has outlived its usefulness. Young earth creationists seem to be trying to affirm the authority and infallibility of Scripture by holding onto it. But they err in assuming the authority of Scripture is undermined if alternative ways of interpreting the genealogies are held. And it seems to me that they undermine their witness of the gospel by insisting their interpretation is the only valid one.

For more articles on creation in the Bible, see the link “Genesis & Creation.”

11/11/16

Help the Medicated Military

© Oleg Dudko | 123rf.com

© Oleg Dudko | 123rf.com

A U.S. Air force pilot was assigned to transport a B-1 bomber from near the Persian Gulf to South Dakota. The trip took nineteen hours and crossed nine time zones. Every four hours, he took a “go pill”—a tablet of Dexedrine. After landing, he went out for dinner and drinks with a friend from the base. When they were driving back to the base, he began hitting his friend, saying that “Jack Bauer” had told him they were going to try and kidnap him. He was eventually charged with auto theft, drunk driving and two counts of assault.  But a court martial judge found him not guilty “by reason of mental responsibility.”

 

 

Four military psychiatrists concluded that Burke suffered from “polysubstance-induced delirium” brought on by alcohol, lack of sleep and the 40 milligrams of Dexedrine he was issued by the Air Force.

In her article for the LA Times, Kim Murphy went on to say a growing number of lawyers are blaming the U.S. military’s heavy use of psychotropics for their client’s aberrant behavior and the related health problems. In 2012 the U.S. Army surgeon general indicated there were almost 8% of active duty Army on sedatives and more than 6% using antidepressants. This was an eightfold increase since 2005.

A former military psychologist said: “We have never medicated our troops to the extent we are doing now … And I don’t believe the current increase in suicides and homicides in the military is a coincidence.” An Army pharmacy consultant said the military’s use of prescription drugs is comparable to the civilian world. “It’s not that we’re using them more frequently or any differently.” Grace Jackson, a former Navy staff, psychiatrist said: “The big difference is these are people who have access to loaded weapons, or have responsibility for protecting other individuals who are in harm’s way.”

According to a 2007 review in Military Medicine, the modern Army psychiatrist’s deployment kit will likely contain “nine kinds of antidepressants, benzodiazepines for anxiety, four antipsychotics, two kinds of sleep aids, and drugs for attention-deficit hyperactivity disorder.” Military doctors believe it would be a mistake to send battalions into combat without these medications, which they see as helping to prevent suicides, calm shattered nerves and help soldiers rest.

Psychiatrist Peter Breggin said that before the Iraq war, soldiers couldn’t go into combat if they were using psychiatric drugs. “You couldn’t even go into the armed services if you used any of these drugs, particularly stimulants,” just 10 or 12 years ago. Now some people are saying psychiatrists won’t approve their deployment unless they take psychiatric drugs.

An Army Pfc. Pleaded guilty to murdering a Taliban commander in Afghanistan. After the death of a good friend, he began hearing a harsh female voice. He was also depressed. He didn’t tell doctors about the voice—only that he was depressed and thinking of suicide. He was prescribed Zoloft for depression and trazodone for sleep. The voices became worse and he began seeing hallucinations of his dead friend. Eventually he walked into the cell of the Taliban commander and shot him in the face. He was eventually sentenced to a ten-year prison term.

Both the American Psychological Association and the American Psychiatric Association in a 2010 hearing urged the Army to stay the course on psychotropic drugs.

Military Times reported that many troops are mixing several different kinds of pills—an antidepressant and an antipsychotic to prevent nightmares, an anticonvulsant or anti-epileptic to prevent headaches. And these medications are being prescribed, consumed and swapped in combat zones. Dr. Grace Jackson said: “It’s really a large-scale experiment. We are experimenting with changing people’s cognition and behavior.”

Data obtained from the Defense Logistics Agency (DLA) showed the DLA spent $1.1 billion on psychiatric and pain medications from 2001 to 2009. The use of psychiatric medication has increased by 76%, with the use of some drug classes more than doubling. Orders for antipsychotic medications were up over 200%; annual spending more than quadrupled from $4 million to $16 million. Anticonvulsant use increased 70%; spending more than doubled from $16 million to $35 million. Spending on antidepressants decreased from $49 million in 2001 to $41 million in 2009, a drop attributed to cheaper generic versions hitting the market during that same time period.

The Army’s highest-ranking psychiatrist told Congress that 17% of the active-duty troops and as much as 6% of deployed troops are on antidepressants. Doctors and lawmakers are questioning whether the drugs are responsible for the spike in suicides within the military—trend that parallels the increase in psychiatric drug use. Dr. Peter Breggin said there was overwhelming evidence that the newer antidepressants commonly prescribed can cause or worsen suicidality, aggression, and other dangerous mental states. “Imagine causing that in men and women who are heavily armed and under a great deal of stress.” But many military doctors believe the risks are overstated and not fully treating depressed troops would be the greater risk.

Military Times said the Defense Department repeatedly denied its requests for copies of autopsy reports that would show the prevalence of these drugs.

From 2001 to 2009, the Army’s suicide rate increased more than 150 percent, from 9 per 100,000 soldiers to 23 per 100,000. The Marine Corps suicide rate is up about 50 percent, from 16.7 per 100,000 Marines in 2001 to 24 per 100,000 last year. Orders for psychiatric drugs in the analysis rose 76 percent over the same period. Other side effects can include increased irritability, aggressiveness and hostility.

Dr. Peter Breggin published an article in Ethical Human Psychology and Psychiatry, “Antidepressant-Induced Suicide, Violence, and Mania: Risks for Military Personnel.”  He noted where the activation side effects of newer antidepressant mimicked the symptoms of PTSD, increasing the hazard when they are prescribed to military personnel. He recommended that the military study the relationship between psychiatric drug treatment and suicide as well as random or personal violence. He also recommended that antidepressant be avoided when treating military personnel. See his website for more information on the relationship between antidepressants, suicide and violence in soldiers.

There is a strong probability that the increasing suicide rates among active-duty soldiers are in part caused or exacerbated by the widespread prescription of antidepressant medication. By themselves, these drugs cause a dangerous stimulant-like profile of adverse reactions. These symptoms of activation can combine adversely with similar PTSD symptoms found so commonly in soldiers during and after combat.

In September 28, 2016, US Senator John McCain introduced the Veteran Overmedication Prevention Act (S. 3410), a companion bill to HR 4640, the Veteran Suicide Prevention Act. Psychologist Philip Hickey reported the bills seek to fight against suicide deaths in military personnel by ensuring that accurate information is available on the relationship between suicides and prescription medication. If passed, these bills would bring information currently being withheld from the public on these relationships. A press release from Senator McCain said:

This legislation would authorize an independent review of veterans who died of suicide or a drug overdose over the last five years to ensure doctors develop safe and effective treatment plans for their veteran patients. We have a long way to go to eradicate veteran suicide, but this legislation builds on important efforts to end the tragedy that continues to claim far too many lives far too soon.

“Data suggests that every 65 minutes a veteran takes his or her own life.” One way to address this is by determining if there is any association between suicide and the medical treatments being received by veterans for service-related conditions. Congressman David Jolly said the following in a press release about his sponsorship of the Veteran Suicide Prevention Act:

Specifically, the Veteran Suicide Prevention Act would require the VA to record the total number of veterans who have died by suicide during the past five years, compile a comprehensive list of the medications prescribed to and found in the systems of such veterans at the time of their deaths, and report which Veterans Health Administration facilities have disproportionately high rates of psychiatric drug prescription and suicide among veterans treated at those facilities.  The VA would then be required to submit to Congress a publicly available report on the results of their review, along with their plan of action for improving the safety and well-being of veterans.

As suggested by Philip Hickey, honor the veterans who have served our country by writing your legislators in the Senate and the House in support of these bills:

Senate: S 3410 – Veteran Overmedication Prevention Act

House: HR 4640 – Veteran Suicide Prevention Act

11/8/16

This Stuff Is not Weed

38945846 - illustration of a not allowed icon with a marijuana leaf

© Juan Pablo Gonzalez | 123rf.com

Like a snowball that begins rolling down from the very top of a hill, negative consequences from synthetic drugs have been building momentum for several years. LiveScience posted an article based on a CDC report that highlighted the increase of synthetic-cannabinoid overdoses. Between 2010 and 2015 there were a total of 456 synthetic-cannabinoid intoxications recorded by 101 US hospitals and clinics included in the study. While the overdoses from these substances are still a fraction of all drug overdoses in the US, their percentage has increased every year since 2010.

The CDC report was based on data gathered from the Toxicology Investigators Consortium (ToxIC), a toxicology surveillance and research tool. The ToxIC Registry was established by the American College of Medical Toxicology in 2010. Of the 456 cases of synthetic-cannabinoid intoxication treated by physicians in the ToxIC, 277 reported synthetic cannabinoids were the only substance used. The findings of the CDC report are representative of what doctors in emergency departments from around the country are seeing.

Among the 456 cases, 70.6% were in persons aged 19-65 and 27.4% were in persons aged 13-18; 83.1% were male. The reported adverse effects were primarily cardiovascular-related (17.0%), pulmonary-related (7.6%) or central nervous system-related (66.1%).  The CNS symptoms included agitation, CNS depression or coma, and delirium/toxic psychosis. The annual percentage of cases increased significantly in all four US Census regions, except the South. “The largest overall increases during these periods took place in the Northeast, primarily driven by increases at the New York City sites.” See the chart below which was taken from the CDC report:

toxicThe CDC report mentioned a June 2015 Morbidity and Mortality Weekly Report (MMWR) for June 12, 2015 that found a 300% increase of telephone calls to poison centers related to synthetic cannabinoid use from January 2015 to April 2015. The report suggested that synthetic cannabinoids posed an emerging public health threat. The number of calls spiked dramatically in mid-April. Look at the report for a chart showing the spike from less than 100 calls per week in the third week of March 2015 to over 500 weekly in the third week of April 2015.

Then there are the “bath salts.” The New York Times published an article referring to Brooklyn users of K2, a synthetic cathinone (bath salts), as “zombies.” In an area around the subway station at Myrtle Avenue and Broadway, emergency workers transported 33 people with suspected K2 overdoses to the hospital in ONE DAY. Brian Arthur, who filmed and then posted what he saw on online said: “It’s like a scene out of a zombie movie, a horrible scene . . . . This drug truly paralyzed people.” While responders helped an unsteady man into an ambulance, another man nearby was slumped against a fire hydrant.

Pairs of police officers walked the blocks around Broadway and Myrtle Avenue, checking the vital signs of men they found unconscious. Anyone who was unresponsive was loaded onto a stretcher and taken away in an ambulance.

Keep in mind this was after legislation by The New York City Council last Fall banned synthetic cannabinoids and threatened businesses and owners who sold K2 with closings, hefty fines and jail time. So it seems that the synthetic drug trade in NYC simply switched to synthetic cathinones.

A 2012 article in the Journal of Medical Toxicology, “The Toxicology of Bath Salts,” provides some background information on the emergence of synthetic cathinones as a drug of abuse. Synthesis of cathinone derivatives occurred as early as the late 1920s. Methcathinone was synthesized in 1928 and mephedrene in 1929. While a few of the derivatives have been investigated for medical use, only bupropion (Wellbutrin, Zyban) have been approved for a medical use in the US and Europe. Wellbutrin is approved to treat depression; Zyban is used as a smoking-cessation aide.

Numerous synthetic cathinone derivatives have become popular for use as “legal highs.” Exactly when these derivatives gained popularity amongst club goers and others seeking new drugs of abuse is difficult to pinpoint, but mentions in Internet drug forums began in 2007.

In “Synthetic Cathinones: A New Public Health Problem,” Karila et al. described the major clinical effects of synthetic cathinones and their impact on public health. Together with synthetic cannabinoids they account for more than two thirds of the New Psychoactive Substances (NPS) available. Again, cardiac psychiatric and neurological adverse effects are the most common ones requiring medical care. “These drugs, still not controlled by international laws, are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine.”

If you’re skeptical about what I’ve written so far, try this article from High Times, “What’s in Synthetic Cannabis and Why Is It So Dangerous?” In order to study the endocannabinoid system in the body, scientists created these compounds for research purposes. The author is quick to point out that synthetic cannabis does not contain cannabis or synthetic cannabinoids. While the compounds bind to cannabinoid receptors in the brain, they only have a “slight relation” to natural THC. “Doctors do not fully understand how most of these compounds interact with the body, and some can be extremely harmful and even deadly.”

The author suggested they would be better named: synthetic cannabinoid receptor agonists (SCRA). THC is only a partial agonist of CB1 and CB2,the cannabinoid receptors, where SCRAs are designed to bind strongly to the receptors and exert THC-like effects. These effects can be 100 times more potent than cannabis. The unusually strong binding of SCRAs to cannabinoid receptors can produce unforeseen downstream effects in the brain and nervous system.

If you consume any of these chemicals, you are literally performing an experiment on your body, and a dangerous one at that. People have suffered from seizures, cardiac arrest, kidney failure, severe reduction in body temperature, etc. and doctors don’t know how it happens or who is more susceptible.

Not only are there many different classes of these compounds, each one of the general classes of compounds contains dozens of different related compounds. “Regulatory agencies play a game of cat and mouse with designer drug manufacturers as they constantly use different compounds to bypass laws.”  While the Us government continues to make different groups of SCRAs illegal, underground chemists seem to be one step ahead, making newer compounds that tend to be more toxic and harmful than the previous generation.

Steer clear of these dangerous substances, treat them like dangerous addictive drugs on par with methamphetamine, ecstasy pills and prescription narcotics. This stuff is not weed, and when your friends smoke it you should confront them about it and make them understand they are putting their lives at risk. Even if you need to pass a drug test, don’t use this stuff; even one toke of Spice can land you in intensive care and put you on a dialysis machine with kidney failure.

Let the fact sink in that what we just reviewed was a clear warning from High Times to avoid synthetic cannabinoids. Alternately, there are synthetic cathinones that can turn you into a zombie. Think about the consequences before you try some.

11/4/16

Who Will Deliver Me?

© albund | stockfresh.com

© albund | stockfresh.com

The last half of the seventh chapter of Romans (7:13-25) has been a matter of theological debate from the time of the early church. Is Paul describing himself while under the law, before salvation or afterwards—his condition under the grace of salvation? The Puritan author John Owen can shed some light on the passage in his seminal work, Indwelling Sin in Believers. In the first chapter of Indwelling Sin, Owen acknowledged the dispute over how to understand the passage, but quickly declared the apostle was describing the condition of the regenerate person, “with respect to the remaining power of indwelling sin.” As if the title wasn’t a dead giveaway.

Clear thinking on this passage is essential, for we live in a time where there are renewed disputes about how to understand the doctrine of original sin. But before turning to Owen’s work, I want to note some of the biblical arguments for both positions. In his New American Commentary: Romans, Robert Mounce said that both positions could be persuasively argued. In support of Paul writing of his experience before conversion in 7:13-25 are several phrases throughout the passage. Paul said he was “sold under sin” (v. 14). He knew that nothing good dwelt in him (v. 18). He was “captive to the law of sin” (v. 23) and a wretched man in need of deliverance (v. 24).

The dramatic contrast of chapter seven with the victory of chapter eight in Romans is further evidence to argue for a preconversion setting. In chapter seven Paul was crying out for deliverance. In chapter eight, he said a believer was set free from the law of sin and death (v. 8:2) and controlled by the Spirit of God (v. 8:9). Another strong argument for Paul describing his spiritual experience before conversion in chapter seven is the “quagmire of impotence and misery” described there. “How could this be the abundant life that Jesus came to bring (John 10:10)?”

On the other hand, throughout the entire passage (7:13-25) Paul used the present tense—over twenty times. For example, in verse fifteen Paul said: “I do not understand my own actions.” If he was speaking of his life before conversion, would he not have said something like: “I don’t understand what I did.” Then there are statements that seem incompatible with the experience of a nonbeliever, as in verse 22: “For I delight in the law of God in my inner being.” Earlier, in Romans Paul said about those who were outside of Christ although they knew God, they sought to suppress the truth of God (1:18-21). There was no one who was righteous, who seeks God (3:10-12).

Mounce said he thought Paul was revealing his difficulty “meeting the radical demands of the Christian faith.” He used his own experience to describe the inevitability of spiritual defeat when a believer fails to trust in Christ for victory over their indwelling sin. Recognizing our inability to live up to our desire to do what is right (chapter 7), we know that in Christ, we are more than conquerors (chapter 8). “Sanctification is a gradual process that repeatedly takes the believer through this recurring sequence of failure through dependency upon self to triumph through the indwelling Spirit.”

Douglas Moo pointed out that most of the early church fathers thought the verses described a preconversion Paul. However, Augustine had a change of heart that seems to have been at least partly due to his battle with Pelagius over the freedom of the will. We see this in his work, A Treatise Against Two Letters of the Pelagians. Augustine wrote this treatise in response to two letters he received from Pope Boniface. One was from Julian and the other from eighteen bishops, including Julian. The letters challenged the catholic faith and attacked Augustine personally. In chapter 22 of book one, Augustine said he once thought that Paul was describing a man under the law (preconversion).

But afterwards I was constrained to give up the idea by those words where he says, “Now, then, it is no more I that do it.” For to this belongs what he says subsequently also: “There is, therefore, now no condemnation to them that are in Christ Jesus.” And because I do not see how a man under the law should say, “I delight in the law of God after the inward man;” since this very delight in good, by which, moreover, he does not consent to evil, not from fear of penalty, but from love of righteousness (for this is meant by “delighting”), can only be attributed to grace.

Almost all of the Reformers, particularly Luther, agreed with Augustine that the passage depicted a believer in Christ.  Writing in the century after the Reformation, Owen was clearly influenced by their thought. His opening declaration was:

It is of indwelling sin, and that in the remainders of it in persons after their conversion to God, with its power, efficacy, and effects that we intend to treat. This also is the great design of the apostle to manifest and evince in chap. 7 of the Epistle to the Romans.

Beginning with verse 7:21, “So I find it to be a law that when I want to do right, evil lies close at hand,” Owen observed four things. First, Paul referred to indwelling sin as “a law.” Second, he experienced this law within himself. Third, despite the inhabitation of this law of sin, the general framework of believers is to do good. And fourth, when the believer would do good, evil is close at hand.

By calling indwelling sin a law, Owen thought Paul meant it was an inward principle that inclines and presses the believer towards actions agreeable and consistent with its own nature, namely that of sin. It is a law in them, but not to them. “Though its rule be broken, its strength weakened and impaired, its root mortified, yet it is a law still of great force and efficacy. There, where it is least felt, it is most powerful.”

In saying he found this law within him, Paul meant that he found it within himself. It is one thing to know in general there is a law of sin. It is entirely another thing to experience the power of the law of sin within your being. Owen saw this experience of the law of sin is the great preservative of divine truth in the soul. When we are taught it from the Scriptures and then find it exists within us, we truly know it. “He shall find the stream to be strong who swims against it, though he who rolls along with it be insensible of it.”

Notwithstanding the indwelling of the law of sin, the habitual inclination of believers is towards good. “There is, and there is through grace, kept up in believers a constant and ordinarily prevailing will of doing good, notwithstanding the power and efficacy of indwelling sin to the contrary.” Good things come from the good treasures of the heart. But you can only see the evidence of this disposition by its fruits. “A will of doing good without doing good is but pretended.”

Whenever a believer would do good, they should consider two things. While there is a gracious principle residing within the will, there is also a contrary principle inclined towards evil. So then, “Indwelling sin is effectually operative in rebelling and inclining to evil, when the will of doing good is in a particular manner active and inclining unto obedience.”

So this is a description of the person who is a believer and a sinner. And “everyone who is the former is the latter also.” Their actions and operations are implied in these expressions: “When I want to do right, evil lies close at hand” (Romans 7:21); and: “For the desires of the flesh are against the Spirit, and the desires of the Spirit are against the flesh, for these are opposed to each other, to keep you from doing the things you want to do” (Galatians 5:17).

Owen then concluded his first chapter for Indwelling Sin as follows:

Awake, therefore, all of you in whose hearts is any thing of the ways of God! Your enemy is not only upon you, as on Samson of old, but is in you also. He is at work, by all ways of force and craft, as we shall see. Would you not dishonour God and his gospel; would you not scandalize the saints and ways of God; would you not wound your consciences and endanger your souls; would you not grieve the good and holy Spirit of God, the author of all your comforts; would you keep your garments undefiled, and escape the woeful temptations and pollutions of the days wherein we live; would you be preserved from the number of the apostates in these latter days;—awake to the consideration of this cursed enemy, which is the spring of all these and innumerable other evils, as also of the ruin of all the souls that perish in this world!

So John Owen and Augustine see Paul speaking of life after conversion. Douglas Moo and others see him remembering his life before conversion. Personally, I find truth in both positions. Experientially, the truth of Owen’s metaphor of swimming against the stream rings true for me. Awareness of the stream of indwelling sin and the strength of its current within me is stronger now than before my conversion. But unconverted, that same stream would have swept me faster downstream, though I was insensible to it. Whether preconversion or postconversion, the answer is still the same: “Who will deliver me from this body of death? Thanks be to God through Jesus Christ our Lord!”

A digital copy of Owen’s work, Indwelling Sin in Believers, is available here.

11/1/16

Ketamine Desperation

© Novic | stockfresh.com

© Novic | stockfresh.com

Jeff wants to smile again and know what happiness is like again. He wants to not feel the urge to kill himself again. He has been hospitalized in psychiatric facilities and has taken a variety of antidepressants and mood stabilizers for his bipolar disorder, but nothing worked. He remained employed as a football analyst until the sky fell in on him and he lost his job. “He was suicidal; so overwhelmed with despair, that he couldn’t even leave his house.” He finally found a treatment option at the Ketamine Clinics of Los Angeles. And so goes one of many testimonies of ketamine’s potential as a rapid treatment for depression.

Steven Mandel MD, the President and founder of the Ketamine Clinics of Los Angeles, is an anesthesiologist who uses ketamine to treat patients who are depressed and suicidal. The standard protocol is to give low dose IV infusions of ketamine. It worked for Jeff. He said, “It’s been remarkable.” His wife looked at him and saw the smile on his face and had the biggest smile herself in response. Jeff thought it was immoral to withhold ketamine from the general public. You can watch a four-minute video on Jeff and Dr. Mandel’s treatment here.

Over the last ten to fifteen years, ketamine has been getting a significant amount of research and media attention as a fast-acting treatment for depression. Reporting for The Washington Post, Sara Solovitch quoted Dennis Hartman as saying: “My life will always be divided into the time before that first infusion and the time after.” But the relief is temporary. “Clinical trials at NIMH have found that relapse usually occurs about a week after a single infusion.”  And it can cause intense hallucinations or a kind of lucid dreaming or dissociative state where some patients lose track of time.

NIMH studies suggest the psychedelic experience with ketamine may play a small but significant role in the drug’s efficacy. Steven Levine, a psychiatrist who has treated 500 patients with ketamine said:

With depression, people often feel very isolated and disconnected. Ketamine seems to leave something indelible behind. People use remarkably similar language to describe their experience: “a sense of connection to other people,” “a greater sense of connection to the universe.”

Hartman travels back-and-forth to an anesthesiologist in New York City for his bimonthly infusions of ketamine. He doesn’t consider himself permanently cured, “but now it’s something I can manage.” In 2012 he helped to found an organization called the Ketamine Advocacy Network, a group that screens ketamine clinics, advocates for insurance coverage and spreads the word on the effectiveness of ketamine to treat depression. The problem is the treatment is not FDA approved. And in higher doses, ketamine is known as the club drug, “Special K.” See previous articles, “Ketamine to the Rescue?” and “Falling Down the K-Hole.”

The promise of ketamine as a fast-acting alternative to other antidepressant medications had led to a growth industry for ketamine clinics around the U.S. and multiple pharmaceutical companies doing their own research into developing ketamine derivatives without the side effects. Ketamine is known to interact with the NMDA receptor involved in learning and memory. So scientists assumed the same receptor was responsible for the anti-depressive action of ketamine. STAT News reported this led to more than a dozen companies trying to develop drugs that target the NMDA receptor. “But these drugs haven’t worked as well as ketamine.” AstraZeneca pulled out of developing its own highly touted ketamine derivative, lanicemine in 2013 when it failed to show long-term benefits.

Iadarola et al. published a 2015 article in the journal Therapeutic Advances in Chronic Diseases that reviewed the growing literature on ketamine efficacy as an antidepressant treatment. They confirmed the temporary effects from ketamine; the effects waned after several days in most patients. The authors suggested that after achieving the antidepressant response from ketamine, the effects could be maintained with intermittent doses of ketamine as described above with Dennis Hartman. Pharmaceutical companies aren’t really interested in moving forward with ketamine infusion since the drug has been long off patent and they can’t make a billion dollar profit on a drug that is off patent. So they seek to develop biosimilars to ketamine.

The latest pharma compound to target the NMDA receptor is esketamine, which Janssen Pharmaceuticals, a division of Johnson & Johnson, is developing as an intranasal spray. Johnson & Johnson announced on August 16, 2016 that the FDA granted esketamine a Breakthrough Therapy Designation. This is the second time esketamine has received a Breakthrough Therapy Designation. The first was in November of 2013. The Breakthrough Therapy Designation is to expedite drug development when a drug demonstrates the potential to be a substantial improvement over available therapies for serious or life-threatening conditions.

But the real excitement may still be ahead. The STAT article cited above reported on a new research study published in the May 26th 2016 issue of the journal Nature that demonstrated a derivative of ketamine could achieve the same benefit, but without the side effects. The study was done on mice, so it has a ways to go in drug development before it can compete with esketamine. Dr. Todd Gould, who led the Nature study, suggested the ineffectiveness of previous studies that targeted the NMDA receptor were because they were looking in the wrong place. His research team showed that the effectiveness of ketamine as an antidepressant doesn’t come from the NMDA receptors—at least not in mice.

In the body, ketamine turns into a molecule called hydroxynorketamine — or HNK — and that molecule is actually what treats the depression. Gould’s team also found that HNK does not interact with the NMDA receptor, and it doesn’t have some of the side effects that ketamine does.

Gould said they have a game plan to move forward with the clinical development of HNK. He and his coauthors have filed a patent application for certain uses of HNK. Outside researchers thought the study was well-done science, but they aren’t convinced it’s time to give up on the NMDA receptor. Their drugs targeting the NMDA receptor are further along in drug development. And they are not convinced they are beating a dead horse just yet. STAT reported that Dr. John Krystal, a psychiatrist and neuroscientist who consults for companies developing NMDA-target drugs said: “In my view, it is quite premature to move away from the hypothesis that NMDA receptor antagonists have antidepressant activity based on this single study.” True, but to you rush to bring your ketamine-like drug to market first?

There will still be the same adverse effects as with ketamine, won’t there? And the temporary nature of the mood elevation is still there, isn’t it? The lack of long-term effects led to the AstraZeneca decision to stop development with lanicemine. And esketamine is “an investigational antidepressant medication, for the indication of major depressive disorder with imminent risk for suicide.” That sounds like a short-term use designation.

Uli Hacksell, chief executive of Cerecor, a Baltimore company that has a Phase 2 drug candidate directed at the NMDA pathway, also took issue with the claim that such drugs might be going after the wrong target, and he said that the paper will have no implications for his company’s development plans. “We think that the clinical data we get with our molecule will speak for themselves,” he said.

One outside researcher, Dr. Francis Collins, the director of the National Institutes of Health (NIH), was quite supportive of Gould’s research. In his NIH Director’s blog, Collins described the background work leading up to the Gould study. He then said:

 HNK appears to come without the side effects of ketamine. After receiving HNK, mice didn’t show changes in their physical activity, coordination, or sensory perception, as is normally seen after a dose of ketamine. HNK also doesn’t appear to have the same potential for abuse either. When given the option, mice will choose to self-administer ketamine, but not HNK.

The new evidence confirms that HNK doesn’t block NMDA receptors like ketamine does. While there’s more to discover about how HNK works, the evidence reveals an important role for AMPA receptors, another type of glutamate receptor in the brain.

Long-term ketamine users can have irreversible urinary tract and bladder problems. Erowid, a pro-drug website, conducted an online survey that indicated there was a clear correlation between total lifetime use of ketamine and the likelihood of reporting bladder/urinary problems. Now these are health problems that occur with higher doses of ketamine than those used to treat depression. Lower doses over the long-term may not have the same adverse effects. However, these known health concerns should not be overlooked in the rush to bring a new fast-acting antidepressant to market. Ketamine (and its derivatives) to the rescue of depression may not turn out to be the super cure some think it is.