03/7/23

Marijuana Policy Has Run Ahead of Science

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Senate Bill 3 was signed into law by Governor Tom Wolf on April 17, 2016, legalizing medical marijuana in Pennsylvania. The Governor anticipated signing the bill “will improve the quality of life for patients and their families throughout Pennsylvania.” Information on the PA Medical Marijuana Program indicated it would include funding for research to study “the use of medical marijuana to treat serious conditions.” There will also be an advisory committee “that will view these research findings and make recommendations to the legislature for changes to the act.” I’d like to suggest they start with a Harvard-based researcher who is concerned that “policy has outpaced science” when it come to making public health decisions about recreational and medical marijuana.

Staci Gruber is an associate professor of psychiatry at Harvard Medical School and the director of the MIND program (Marijuana Investigations for Neuroscientific Discovery). She has done research on the effects of both recreational and medical marijuana. In an interview with The Harvard Gazette, Dr. Gruber said the science on the health effects of marijuana is not yet settled. “When we think about legalization we always like to have science inform policy. In this particular case, it seems to me that policy has outpaced science.”

She added there is a lot we don’t know about the effects of marijuana. Most of what we do know comes from studies of “chronic, recreational marijuana users.” There are differences between recreational and medical marijuana use, for example with regard to what they use, and how they use. She said there has been well-founded excitement about the potential for medical cannabis use. “[But] there’s a striking paucity of research on the use of medical cannabis.”

Dr. Gruber and her colleagues discussed the findings in a study of theirs, “Splendor in the Grass?” that looked at the impact of medical marijuana on executive functioning. They acknowledged how the growing body of evidence shows recreational marijuana use adversely effects brain function, especially during adolescence, the critical period of neurodevelopment. But they also theorized the use of medical marijuana (MMJ) may not lead to the same adverse neurocognitive effects. Recreational users, seeking a euphoric, mood altering effect, use products with a high THC content. In contrast MMJ users seek medical relief and use products with a markedly different chemical composition than common recreational products. “These MMJ products are often (but not always) high in other cannabinoids, such as cannabidiol (CBD) which has been touted for its therapeutic potential, and which is not psychoactive.”

The study found that after three months of medical marijuana use, patients (who had previously not been exposed to marijuana) experienced some improvement, rather than the well-documented deficits. “They showed some improvements in measures of executive functions. They also had some improvements in sleep quality and some measures of mood and quality of life.” A subset of people who were using MMJ for chronic pain also reported improvements. Although it was a small sample size, there was a 42% reduction in opiate use. When they analyzed samples of their patient’s products, a number of them were using products high in CBD (cannabidiol) and other non-psychoactive cannabinoids.

Gruber thought there was hope for at least adjunctive therapy, “if not substitution therapy,” for cannabinoids or cannabinoid-based products for individuals currently using opioids. “We’ve seen individuals who’ve stopped using opioids altogether.” That won’t work for everyone. “But that doesn’t mean it’s something that shouldn’t be exploited and explored.”

While future studies are needed to further examine the impact of MMJ, research is impeded by a number of federal and state restrictions. It is imperative, however, that sound research, including well-controlled clinical trials of MMJ products, many of which are already widely used by patients, are thoroughly examined. As the “green rush” pushes forward, gaining momentum as states continue to adopt less restrictive policies, we cannot afford for research to continue to lag behind.

Dr. Gruber said her goal as a scientist was to provide truthful information so all people, regardless of their recreational or medical status, can understand what is in their cannabis or medicine. In pursuit of this goal, Dr. Gruber and her colleague Kelly Sagar continued a discussion of their research with “Marijuana on the Mind?” in Policy Insights from the Behavioral and Brain Sciences. You can also watch an archived webinar by Gruber and Sagar on the same subject, “Marijuana on the Mind: A Primer for Policymakers” on the website Social Science Space, where there are also written answers to some of the questions from the webinar. The presentation exists as an independent YouTube video as well. The audio cuts out a few times, but returns if you continue with the video.

In “Marijuana on the Mind?” Gruber and Sagar gave a helpful review of the history of medical use of marijuana, noting how it was included in the U.S. pharmacopeia (a list of medicinal drugs with their effects and directions for their use) until 1942. They also documented several areas of concern with marijuana, including its adverse effects on cognition, especially executive function and memory; brain development among adolescents; and safety concerns related to the frequency and magnitude of marijuana use as well as its potency.

Marijuana (MJ) use negatively effects executive brain functions (EF) such as attention, decision making, risk taking, inhibition and verbal fluency. An earlier age of onset in using MJ appears to be related to greater impairment on EF. “Several investigations have also noted that lower EF appears to predict increased MJ use.” Several aspects of memory are negatively effects by MJ use. Some evidence suggests increased use and higher exposure to MJ are related to slower psychomotor/processing speed.

The formation of grey matter and whiter matter in the brain is adversely effected by MJ use. Grey matter is responsible for information processing and decision-making. White matter has a critical role in promoting efficient communication within and between regions of the brain. Adolescent MJ users are particularly vulnerable to grey matter reductions; minimal further damage seems to occur after early adulthood. Lower white matter integrity is related to higher impulsivity scores, particularly with early onset MJ users.

MJ users with early onset (prior to age 16) reportedly use MJ nearly twice as often and more than 2.5 times as much relative to late-onset users. Overall, frequency and duration of use appear to be key factors in determining the extent of MJ-related impairment.

Safety concerns with MJ use are on the rise due to the increased potency of marijuana and the use of MJ concentrates. The potency of marijuana has risen nearly 200% since 1995. The use of concentrated MJ products, such as dabs, shatter, wax, budder and others can exceed 60% THC. “Furthermore, these products may also contain residual amounts of solvents (i.e., butane, hexane), often used to make concentrates, which are potentially toxic.” There has been very little research done on cognitive performance or measures of brain structure and function in humans with MJ concentrates. “This raises concern that adverse consequences associated with MJ use may be worse now than in the past, particularly among young users.”

Based upon their discussion, policy recommendation given by Gruber and Sagar include:

  1. age restrictions based upon evidence highlighting the developmental trajectory of the adolescent brain;
  2. restrictions on targeting youths in advertisements;
  3. safe packaging guidelines to prevent the accidental ingestion of edible MJ products by children;
  4. place limits on THC potency as well as minimums for potentially beneficial cannabinoids in marijuana, like CBD;
  5. more research on the impact of medical marijuana, which will likely require a lessening of marijuana as a Schedule I substance

As the dialogue regarding legalization of recreational and MMJ continues, perceived risk of MJ use has fallen to an all-time low. Consequently, those with the highest neurodevelopmental vulnerability are using MJ more frequently than in previous years, posing a serious public health issue. A growing body of evidence indicates that relative to non-MJ users, heavy MJ users exhibit poorer performance on cognitive tasks, altered patterns of brain activity, and lower frontal WM coherence, which are highly moderated by age of onset of MJ use. Given the potential therapeutic benefits of MJ, however, it is important to weigh these risks with the benefits. Policy has outpaced science, and eased restrictions allowing citizens to use MJ, in some cases without the benefit of appropriate research. Additional investigation is warranted and necessary to guide informed policy decisions. As states consider legislation for MJ use, it is imperative to determine safe guidelines regarding the impact of MJ on the brain, particularly during critical periods of neurodevelopment.

Dr. Gruber’s research through the MIND program will be extremely helpful for the PA Medical Marijuana Program and state policy makers, such as members of the advisory committee, in making informed public policy decisions with the ongoing availability of medical marijuana in Pennsylvania. The review by Gruber and Sagar of the research relevant the influence of marijuana on cognition, brain structure and brain function in “Marijuana on the Mind?” can be helpful in making future public policy decisions with regard to medical marijuana in the state.

An article cited by Gruber and Sagar, “Cannabis for Medical Use,” should also be reviewed by policy makers, as it is a systematic review and meta-analysis of the benefits and adverse events of cannabinoids. The full text of the systematic review is available. What follows is from the article’s Discussion.

Most studies suggested that cannabinoids were associated with improvements in symptoms, but these associations did not reach statistical significance in all studies. Based on the GRADE approach, there was moderate-quality evidence to suggest that cannabinoids may be beneficial for the treatment of chronic neuropathic or cancer pain (smoked THC and nabiximols) and spasticity due to MS (nabiximols, nabilone, THC/CBD capsules, and dronabinol). There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy (dronabinol and nabiximols), weight gain in HIV (dronabinol), sleep disorders (nabilone, nabiximols), and Tourette syndrome (THC capsules); and very low-quality evidence for an improvement in anxiety as assessed by a public speaking test (cannabidiol). There was low-quality evidence for no effect on psychosis (cannabidiol) and very low-level evidence for no effect on depression (nabiximols). There was an increased risk of short-term AEs with cannabinoid use, including serious AEs. Common AEs included asthenia, balance problems, confusion, dizziness, disorientation, diarrhea, euphoria, drowsiness, dry mouth, fatigue, hallucination, nausea, somnolence, and vomiting. There was no clear evidence for a difference in association (either beneficial or harmful) based on type of cannabinoids or mode of administration. Only 2 studies evaluated cannabis.There was no evidence that the effects of cannabis differed from other cannabinoids.

The authors noted there was moderate-quality evidence to support the use of cannabis to treat chronic pain and spasticity. However, the existing evidence suggesting improvements in nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome was low quality evidence. Cannabinoids were also associated with an increased risk of short-term adverse events such as those noted in the above quote. Future studies with large random clinical trials were said to be needed in order to confirm the effects of cannabinoids with issues such as: weight gain in patients with HIV/AIDS, depression, sleep disorders, anxiety disorders, psychosis, glaucoma, and Tourette syndrome. Additionally, the lack of research into the effects and adverse events with cannabis point to the need of future studies in these areas.

Hopefully as medical marijuana becomes more widely available in Pennsylvania, the administrators of the Medical Marijuana Program and other state policy makers will pursue the recommendations suggested in the research reviewed here by Gruber and others who are concerned that “policy has outpaced science” when it comes to lawmakers making public health decisions about recreational and medical marijuana.

Originally posted on March 6, 2018.

08/16/22

Reinhold Niebuhr and the Serenity Prayer

Heath Union Church, Heath MA

In May of 1943 Reinhold Niebuhr completed teaching his classes at Union Theological Seminary and left for a two-month series of meetings, conferences and lectures in England and Scotland. The German Axis forces in North Africa surrendered on May 12, 1943. Four days later, German troops crushed the last resistance in the Warsaw Ghetto Uprising, killing thousands of Jews. The rest were sent to Treblinka. Soon after Niebuhr returned to his family in Heath Massachusetts, Allied troops landed in Sicily on July 10th. On July 24th, the Allies began bombing the German city of Hamburg. By July 25th, Mussolini was overthrown and the new Italian government began peace talks. Somewhere in the midst of these earth-shaking events, Niebuhr preached a sermon at the Heath Union Church and uttered what would become known as the Serenity Prayer for the first time.

The above-described origins of the Serenity Prayer were given by Elisabeth Sifton, the daughter of Reinhold Niebuhr, in her book: The Serenity Prayer. Sifton deftly placed its origins in the midst of the work and ministry of her father during WW II. She said at some point in late 1943 or early 1944, a friend of her father’s, Howard Robbins suggested this little prayer about “grace, courage and wisdom” would be appropriate for inclusion in material he was preparing for army chaplains in the field. Niebuhr gave Robbins a copy of the prayer, and in 1944 it was included in the Book of Prayers and Services for the Armed Forces.

This was its first publication in any form and in any language, and its because of this little booklet that eventually it became famous. . . . A short while later Alcoholics Anonymous, then a fledgling small organization scarcely a decade old, with my father’s permission, also started to use the prayer in their regular meetings.

Sifton said she doesn’t know when or how A.A. simplified the text of her father’s original version of the Serenity Prayer. And although he let it happen “and didn’t fuss when the wordings were altered,” he did mind the changes. But Niebuhr never copyrighted his prayer. Sifton said it was inconceivable to him to construe prayers as a source of revenue. So he could not and did not control its misquotation, misattribution or embellishment.  The original text for Niebuhr’s Serenity Prayer is followed by the shortened A.A. version, and one of the longer versions.

Niebuhr’s 1943 version: “God give us grace to accept with serenity the things that cannot be changed, courage to change the things that should be changed, and the wisdom to distinguish the one from the other.”

The AA version appears in the Third Step essay of the A.A. book, The Twelve Steps and Twelve Traditions: “God grant me the serenity to accept the things I cannot change, courage to change the things I can, and the wisdom to know the difference.”

One version of the so-called “Complete” Serenity Prayer is in the linked article below by Nell Wing, an A.A. archivist. It is as follows:

God, grant me the Serenity to accept the things I cannot change; Courage to change the things I can, and the Wisdom to know the difference. 

Living one day at a time; enjoying one moment at a time; accepting hardship as the pathway to peace. Taking, as He did, this sinful world as it is, not as I would have it. Trusting that He will make all things right; if I surrender to his Will; that I may be reasonably happy in this life, and supremely happy with Him forever in the next. Amen. 

Elisabeth Sifton said she has no idea where the additional clauses of the “complete” version came from. But their message and tone were not in any way “Niebuhrian.” She noted how the A.A. version simplified the opening and framed the prayer in the first person singular, rather than the first person plural of her father’s original text. It also omitted the spiritually correct, but difficult idea of praying for “grace to accept with serenity that which we cannot change.” Instead, it focused on the simpler idea of obtaining “serenity to accept what cannot be changed.”

Nell Wing, an A.A. Archivist, wrote a paper in 1981: “Origin of the Serenity Prayer.” There she described several different purported “origins” for the Serenity Prayer that A.A. was told over the years. Bill W. and A.A. have attributed their initial discovery of the Serenity Prayer to Niebuhr, but still seem to repeat information about it that conflicts with Sifton’s above-described version—which was told to her by her parents. For example, A.A. attributes their initial discovery of the (then) anonymous prayer to an obituary found by an early A.A. member in a New York paper in June of 1941. The connection to Dr. Niebuhr didn’t come to A.A.’s attention until the late 1940s.

Wing said an A.A. member reported seeing the prayer in Reinhold Niebuhr’s writings, “as if it were original to him.” She also quoted from a 1951 letter by an A.A.  member to Bill W. The man had been in contact with Dr. Niebuhr, who confirmed that he did write the prayer and that it had been distributed to soldiers during WWII. Bill W. responded by saying that it was probable the Serenity Prayer existed in some form or other before Dr. Niebuhr. “Now it is pretty certain that Dr. Niebuhr did write the prayer in its present form and we also have on file a letter from him to that effect.” Bill then referenced a September 1950 article by Jack Alexander, which Wing quoted:

Originally thought in Alcoholics Anonymous to have been written by St. Francis of Assisi, it turned out on recent research to have been the work of another eminent nonalcoholic, Dr. Reinhold Niebuhr, of Union Theological Seminary. Dr. Niebuhr was amused on being told of the use to which his prayer was being put. Asked if it was original with him, he said he thought it was, but added, “Of course, it may have been spooking around for centuries.” Alcoholics Anonymous seized upon it in 1940 [actually 1941], after it has been used as a quotation in the New York Herald Tribune. The fellowship was late in catching up with it; and it will probably spook around a good deal longer before the rest of the world catches up with it.”

Wing also referred to several other “origins” of the prayer that have been sent to A.A. at one time or another. There was even the reprint of a letter written by Ursula Niebuhr, Reinhold’s wife, which briefly reviewed the background to the Serenity Prayer given above by her daughter.

In the January 1950 issue of the AA Grapevine, there appeared an article entitled: “The Serenity Prayer,” that attributed the prayer to Niebuhr, and even gave what they said his original text. The prayer attributed to Niebuhr in the Grapevine article was not the version quoted above as the Niebuhrian 1943 version. The A.A. article also dated the origin of the Serenity Prayer to 1932. Howard Robbins is said to have received permission to place it in a compilation of prayers he then published in 1934. An A.A. member saw the prayer in an obituary in 1939, and brought it to the attention of Bill W. and others in A.A. The history described here seems to contradict that given above by Sifton. For more on the A.A. understanding of the origins of the Serenity Prayer, see: “The Serenity Prayer and A.A.

Elisabeth Sifton, her mother and father all seem to have a similar sense of the Niebuhrian version of the Serenity Prayer coming from a sermon that he preached at Heath during WWII. Nell Wing reviewed several other possibilities, some of which were shown to be false. Yet the consensus from A.A. seems to believe the 1943 Niebuhrian version wasn’t the first. Writing for the Yale Alumni Magazine in 2008, Fred Shapiro wrote of his own investigations into the origins of the Serenity Prayer, “Who Wrote the Serenity Prayer?”

Shapiro noted that Niebuhr’s version of the Serenity Prayer was selected by the editor’s of the World Almanac as one of the ten most memorable quotes of the last 100 years. In English and German-speaking countries, he thought it was probably the only prayer to rival the Lord’s Prayer in popularity. Shapiro said Niebuhr himself said it was possible he assimilated its concept from some earlier, forgotten source. Nevertheless, Niebuhr made it clear that he believed the prayer originated with him.

Shapiro’s research found versions of the Serenity Prayer in newspaper databases before 1943. He stated how the evidence was by no means, conclusive; and it is entirely possible Niebuhr composed the prayer much earlier than he himself remembered. When he found at least eight versions of the prayer in newspapers before 1943, he contacted Elisabeth Sifton with his evidence. In response, Sifton commented that prayers evolve, are borrowed, transmuted and revised—by their original writers and others.

Sifton herself noted in her own book where the ideas expressed in the Serenity Prayer existed in previous works by her father. She noted how the tone of the Serenity Prayer radiated throughout Niebuhr’s classic work, The Nature and Destiny of Man. Niebuhr gave a series lectures with the same name at the Gifford Lectures between 1938 and 1940 at the University of Edinburgh. She pointed out where the second volume ended with a consideration of the ideas he was to express in his little prayer just a year or so later:

Wisdom about our destiny is dependent upon a humble recognition of the limits of our knowledge and our power. Our most reliable understanding in the fruit of “grace,” in which faith completes our ignorance without pretending to possess its certainties as knowledge, and in which contrition mitigates our pride without destroying our hope.

The following are two examples of what Shapiro found. Follow the above link to his full article for more.

In the January 16, 1936 edition of the Syracuse Herald, the executive secretary for the Syracuse Y.W.C.A. quoted the following prayer in her annual report:

O God, give us courage to change what must be altered, serenity to accept what cannot be helped, and insight to know the one from the other.

In the February 19, 1939 edition of the Ada (Oklahoma) Herald the home counselor for Oklahoma City’s public schools prayer said the prayer for both parents should be:

Oh God, give me serenity to accept that which cannot be changed, give me courage to change that which can be changed and wisdom to tell the one from the other.

Shapiro said it was possible that Niebuhr introduced the prayer by the mid-1930s in an unpublished or private setting. It was then quickly disseminated with his identification largely forgotten. But he said it must be asked why Niebuhr himself never suggested he had used the prayer in the 1930s. However, he believes a second alternative is more likely. The prayer really was “spooking around for years” and Niebuhr unconsciously adapted it from some already-existing formulation.

Sifton responded to Shapiro’s conclusions in “It Takes A Master to Make A Masterpiece.” You can find her response at the end of the link for Shapiro’s article, “Who Wrote the Serenity Prayer?” She still affirmed her father as the essential author of the Serenity Prayer. Shapiro merely demonstrated that her father’s voice reached far more American churches and organizations than they had previously realized. Prayers are presented orally and become famous orally long before they are put on paper.

Yet the great masterpiece prayers don’t materialize in some random, bubble-up way, either: their power comes from a distillation of complex spiritual truths, and for this we need authors, we need the tradition’s most gifted practitioners. In my book, I quoted prayers from various sources that my father knew well and whose cadences and theology feed into the Serenity Prayer’s concise wisdoms, because I wanted to suggest how the rich texture of worship as experienced by generations of believers nourishes the creation of new prayers. To throw light on this long, often anonymous process was one purpose of my book.

Sifton commented that since the Serenity Prayer has become so associated with the 12 Steps of Alcoholics Anonymous, most people think of it as expressing what we must work on within our “personal self-improvement projects.” Yet it was composed in wartime. It addresses “the inconsolable pain, loss, and guilt that war inflicts on the communities that wage it.”

She said her father drafted his prayers rapidly, or composed them right on the spot, rewording them many times before he felt they were in final form. Most of the prayers she cited in her book were not published until after his death in 1971. But by then generations of student and worshipers had known them well and used them for decades. “The Serenity Prayer was unusual in his oeuvre [body of work], then, only in the odd circumstance of its wartime publication and subsequent diffusion.”

The Niebuhrian version of the Serenity Prayer seems to have clearly come from Reinhold Niebuhr’s 1943 sermon. It also seems likely that the concepts within the prayer had been part of his teaching, thinking and writing in the years prior to that fateful sermon. And yet, religious believers and philosophers for thousands of years have struggled to be at peace or in harmony with the things in life that cannot be changed; to find courage to change the things they can; and to know the one from the other. The dilemma of the Serenity Prayer strikes at the heart of all religious and philosophical quests to know the will of God. Lord, by your grace grant us the serenity, courage and wisdom to know and do your will.

Originally posted on 01/17/2017

10/16/18

Feuding Ideologies, Part 1

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In August of 2017, the now former Health and Human Services Secretary, Tom Price, said he didn’t think it was necessary to declare the opioid epidemic to be a national emergency. This was despite the president’s own opioid commission recommending it as the “first and most urgent recommendation.” Two days later, the President reversed Price’s statement, saying: “The opioid crisis is an emergency, and I’m saying officially right now it is an emergency.” The response was mixed. While President Trump’s announcement could be used to help free up federal resources and help to prioritize responses to the disaster, it could also permit the administration to push for new sentencing legislation in order to get “tough on crime” related to drug use.

What isn’t disputed is that the U.S. does have a serious opioid problem and something needs to be done about it. Drug overdose is the leading cause of death in Americans under the age of fifty. Forecasts by STAT News are the annual death rate will increase by at least 35 percent by 2027. The CDC reported that from 2002 to 2015 there was a 5.9-fold increase in the overdose deaths from heroin and non-methadone synthetic opioids.

The latest statistics for the U.S. opioid epidemic is now available in the 2016 National Survey on Drug Use and Health (NSDUH). Among the myriad of statistics reported there was news that heroin users increased 230% from 2002 to 2016, while heroin deaths increased 630%. An estimated 948,000 people aged 12 or over reported they used heroin in the past year. That translates to .4% of the country’s population. There were also an estimated 11.5 million people who misused pain relievers in the past year, 4.3% of the population aged 12 or over. Combined, there are 11.8 million people who misused opioids, 4.4% of the population, in 2016.

The 2016 NSDUH Report can be accessed here. A shorter, graphic-based report of key findings, including those noted above, is here.

One of the treatment approaches often touted to address the opioid crisis is medication-assisted treatment (MAT) with Suboxone. In January of 2015, Jason Cherkis wrote “Dying To Be Free.” His subtitle asked why we weren’t using a treatment for heroin addiction—Suboxone—that actually worked. The opioid problem in Kentucky was the focus of his article, which I found to be rhetorically persuasive and well written. You are introduced to individual after individual who wouldn’t or couldn’t use Suboxone and ended up dead from an eventual overdose.

“Dying To Be Free” was a finalist for a Pulitzer in 2016 for its “deeply researched reporting on opioid addiction” that showed how many drug overdose deaths could have been prevented. The cover letter submitted for its entry for the Pulitzer by The Huffington Post said it triggered a series of state and federal policy changes that rejected abstinence for opioid misuse and embraced medication-assisted treatment. “‘Dying To Be Free’ offered readers an immersive experience that included audio and video documentaries and photo and data displays.”

This was not fake news. “Dying to Be Free” captured the agony of individuals and families who struggle with opioid misuse. But it also made abstinence-based approaches to treatment and recovery a bogeyman responsible for many of the unnecessary deaths from opioid overdoses. The rhetoric of the article was a straw man attack on abstinent-based treatment while it extolled MAT. Its biomedical treatment bias seemed to dismiss or ignore many of the problems with Suboxone as a MAT for opioid addiction. Nor did it tell the whole story behind Suboxone. It also misrepresented the recovery philosophy of self-help groups like Alcoholics Anonymous. Here’s what I mean.

In the last paragraph of his second chapter, Cherkis said: “There’s no single explanation for why addiction treatment is mired in a kind of scientific dark age, why addicts are denied the help that modern medicine can offer.” This succinctly captures the problem as he sees it with existing treatment approaches to the opioid crisis. Heroin addiction is a medical disease and should be treated as a medical disease. Modern medicine has a scientific treatment for heroin addiction that is resisted because of stigma, a deep-rooted adherence to self-help, and the criminalization of heroin addiction. If you question or oppose MAT, you are apparently mired in a kind of scientific dark age.

To enter the drug treatment system, such as it is, requires a leap of faith. The system operates largely unmoved by the findings of medical science. Peer-reviewed data and evidence-based practices do not govern how rehabilitation facilities work. There are very few reassuring medical degrees adorning their walls.

Dr. Mary Kreeft, one of the pioneers of methadone maintenance, was liberally quoted to support the medical model of addiction. She noted how opioid addiction alters multiple regions in the brain, including those that regulate reward, memory, learning, stress, hormonal response and stress sensitivity. According to Dr. Kreeft, after a long cycle of opiate addiction, a person needs specific medical treatment. Some people may be OK in time. But “the brain changes, and it doesn’t recover when you just stop the drug because the brain has been actually changed.”

An abstinence-only treatment that may have a higher success rate for alcoholics simply fails opiate addicts. “It’s time for everyone to wake up and accept that abstinence-based treatment only works in under 10 percent of opiate addicts,” Kreeft said. “All proper prospective studies have shown that more than 90 percent of opiate addicts in abstinence-based treatment return to opiate abuse within one year.” In her ideal world, doctors would consult with patients and monitor progress to determine whether Suboxone, methadone or some other medical approach stood the best chance of success.

This is a rigid, strict medical model of opioid addiction. And it gives a mixed message regarding whether or not the individual will ever be able to stop taking Suboxone or methadone. Neither drug, said Cherkis, is a miracle cure. But they buy addicts time to fix their lives, seek counseling and allow their brains to heal. So far, so good. But here comes the caution: Doctors recommend tapering off the medication cautiously. The process could take years, as addiction is a chronic disease and effective therapy takes time. Then comes the typical analogy of the pure medical model of addiction:

Doctors and researchers often compare addiction from a medical perspective to diabetes. The medication that addicts are prescribed is comparable to the insulin a diabetic needs to live.

There is no mention of neuroplasticity—the brain’s ability to reorganize itself by forming new neural connections. “Neuroplasticity allows the neurons (nerve cells) in the brain to compensate for injury and disease and to adjust their activities in response to new situations or to changes in their environment.”

Jeffrey Schwartz and Rebecca Gladding use an almost identical description of neurological action to that given above by Dr. Kreeft to describe how to change the brain; to modify bad habits (including addiction) and unhealthy thinking. In You Are Not Your Brain, they describe how we teach our brains to act in unhealthy ways. The brain does not distinguish between beneficial and destructive habits, “it just responds to how you behave and then generates strong impulses, thoughts, desires, cravings, and urges that compel you to perpetuate your habit, whatever it may be.”

Clearly, the brain can exert a powerful grip on one’s life—but only if you let it. The good news is that you can overcome the brain’s control and rewire your brain to work for you by learning to debunk the myths it has been so successfully selling you and by choosing to act in healthy, adaptive ways.

Neuroplasticity, as described by Schwartz and Gladding, does not reject Kreeft’s neurological description of addiction.  But it does say it isn’t the whole story. An ideology of addiction as a purely biomedical condition seems to permeate “Dying To Be Free.” Addiction, when conceived strictly as a brain disease, rejects or ignores the non-scientific construct of mind. If we are conceived as only biological beings, then addiction is explained and treated within a biomedical worldview. Any treatment approach to addiction not based on this premise is therefore faulty.

Drug treatment facilities were said in “Dying To Be Free” to “generally” fail to distinguish between addictions. They have a one-size-fits-all approach.  Addicts in residential treatment experience a “hodgepodge” of drill-instructor tough love and self-help lectures. Programs appear simultaneously excessively rigid and wildly disorganized. “And with roughly 90 percent of facilities grounded in the principle of abstinence, that means heroin addicts are systematically denied access to Suboxone and other synthetic opioids.”

After describing two older, drug treatment programs with a therapeutic community model of care that used coercive techniques—Synanon and Daytop (Drug Addicts Yield TO Persuasion)— he said:

The number of drug treatment facilities boomed with federal funding and the steady expansion of private insurance coverage for addiction, going from a mere handful in the 1950s to thousands a few decades later. The new facilities modeled themselves after the ones that had long been treating alcoholics, which were generally based on the 12-step methodology. Recovering addicts provided the cheap labor to staff them and the evangelism to shape curricula. Residential drug treatment co-opted the language of Alcoholics Anonymous, using the Big Book not as a spiritual guide but as a mandatory text — contradicting AA’s voluntary essence. AA’s meetings, with their folding chairs and donated coffee, were intended as a judgment-free space for addicts to talk about their problems. Treatment facilities were designed for discipline.

In support of this claim, Cherkis referred to a 2012 study conducted by the National Center on Addiction and Substance Abuse at Columbia University. It apparently was a reference to “Addiction Medicine: Closing the Gap between Science and Practice.” He said the study concluded the U.S. treatment system was in need of a “significant overhaul” and questioned whether the low levels of care received by addiction patients constituted a from of medical malpractice.

While medical schools in the U.S. mostly ignore addictive diseases, the majority of front-line treatment workers, the study found, are low-skilled and poorly trained, incapable of providing the bare minimum of medical care. These same workers also tend to be opposed to overhauling the system. As the study pointed out, they remain loyal to “intervention techniques that employ confrontation and coercion — techniques that contradict evidence-based practice.” Those with “a strong 12-step orientation” tended to hold research-supported approaches in low regard.

The Columbia University study did state a significant overhaul was needed in current treatment approaches; and it raised the question if the insufficient care received by addiction patients constituted “a form of medical malpractice.” It also pointed to the need for medical schools to “educate and train physicians to address risky substance use and addiction.” Unsurprisingly, it went on to say that all aspects of stabilization and treatment with addictions should be managed by a physician “as is the case with other medical diseases.” Remember that the Columbia study and Cherkis were both advocating for a physician-centered, medical model approach to addiction treatment.

However, I couldn’t find where it was supposed to have said the majority of front-line treatment workers were low-skilled and poorly trained. There was a section stating that physicians and other health professionals should be on the front line addressing addiction. Then it said: “Paraprofessionals and non-clinically trained and credentialed counselors can provide auxiliary services as part of a comprehensive treatment and disease management plan.”

It did not say the majority of front-line treatment workers were low-skilled and poorly trained “incapable of providing the bare minimum of medical care.” Yet in the case study examples found in “Dying To Be Free,” that is what Cherkis presented. The Columbia study did cite another study, which found that recovering support staff had little enthusiasm for evidence-based practices. “They also were more likely to support intervention techniques that employ confrontation and coercion–techniques that contradict evidence-based practices.” But these paraprofessionals only made up “24 percent of the treatment provider workforce.”

Cherkis seems to have mis-remembered what the Columbia study actually claimed in this matter. I wonder if, because of his commitment to a strictly medical model ideology for opiate treatment, he was reading into the study. His quote above supported the description of the treatment facilities he highlighted in his article, but wasn’t found by me in the article he cited on the Columbia study.

Another example of how his treatment ideology distorted his portrayal of Suboxone treatment was with how he described Hazelden’s Suboxone treatment program. “Dying To Be Free” mentioned that Hazelden, now the Hazelden Betty Ford Foundation, developed its own Suboxone treatment program for opioid addicts. But it failed to note this wasn’t accompanied by a rejection of “Twelve Step practices.” Within “The History of Hazelden,” on the Hazelden Betty Ford Foundation website, was the statement of how it “integrates the cornerstone Twelve Step practices of mutual support along with multidisciplinary clinical care, evidence-based therapies and the latest research in brain science.” Why weren’t there some case study examples from Hazelden in “Dying To Be Free”?

The facilities Cherkis highlighted in Kentucky were not representative of abstinent-based addiction treatment centers in the U.S.; ones that use the 12 Steps to structure their treatment program. In reading “Dying To Be Free” I see an underlying ideology of conceiving and treating addiction, specifically opiate addiction, through a strict biomedical lens. That is not the whole story of addiction. As a result, the rhetoric of the article constituted a straw man attack on abstinent-based treatment while it extolled MAT. This bias presents readers with an implied choice, a dichotomy, between Suboxone as an MAT for addiction and 12 Step, abstinent-based treatment. Ironically, Hazelden, an historically important treatment center that pioneered 12 Step, abstinence-based treatment, did not choose MAT over the 12 Step-based treatment, but combined the two. But you don’t get that information in “Dying To Be Free.”

Part 2 and Part 3 of this article will look at how “Dying To Be Free” misrepresented the recovery philosophy of self-help groups like Alcoholics Anonymous; and skimmed over the problems with MAT, specifically Suboxone.

03/27/18

Kratom Regulation is Coming

© Noppharat Manakul | 123rf.com; close up of a mitragyna speciosa (kratom) leaf

February of 2018 was not a good month if you are pro-kratom. The FDA released information on adverse events and “even stronger evidence of kratom compounds’ opioid properties.” Then the CDC announced a multistate outbreak of Salmonella infections related to kratom. Then FDA announced the destruction and recall of kratom products. And the icing on the kratom cake was the FDA stating the agency has seen their death count related to kratom increase from 36 to 44.

The February 6th statement regarding additional adverse events associated with kratom said the agency used the PHASE (Public Health assessment via Structural Evaluation) methodology to simulate how the chemical elements of kratom are structured at a molecular level, how they behave inside the body and what they potentially do to the brain. In other words, PHASE used the molecular structure of a kratom to predict how it could biologically function in the body. “The new data provides even stronger evidence of kratom compounds’ opioid properties.” The 25 most prevalent compounds in kratom all share structural similarities with controlled opioid substances such as morphine derivatives.

The model predicted that 22 (including mitragynine) of the 25 compounds in kratom bind to mu-opioid receptors. This model, together with previously available experimental data, confirmed that two of the top five most prevalent compounds (including mitragynine) are known to activate opioid receptors (“opioid agonists”).

Additionally, the computational model predicted some kratom compounds may bind to receptors in the brain thought to contribute stress responses contributing to neurologic function in seizures and cardiovascular function in respiratory depression. And the FDA “found that kratom has a strong bind to mu-opioid receptors, comparable to scheduled opioid drugs.” What all this means is that:

The data from the PHASE model shows us that kratom compounds are predicted to affect the body just like opioids. Based on the scientific information in the literature and further supported by our computational modeling and the reports of its adverse effects in humans, we feel confident in calling compounds found in kratom, opioids.

Kratom-related deaths have increased to 44, according to the FDA. The agency said they could not fully assess many of the cases because of limited information. Additionally, some of the cases with fatal outcomes indicate kratom was not the only substance used. “Cases of mixing kratom, other opioids, and other types of medication is extremely troubling because the activity of kratom at opioid receptors indicates there may be similar risks of combining kratom with certain drugs, just as there are with FDA-approved opioids.” Particularly troubling was a new report of death where the individual had no known history of toxicologic evidence of opioid use except kratom.

Taken in total, the scientific evidence we’ve evaluated about kratom provides a clear picture of the biologic effect of this substance. Kratom should not be used to treat medical conditions, nor should it be used as an alternative to prescription opioids. There is no evidence to indicate that kratom is safe or effective for any medical use. And claiming that kratom is benign because it’s “just a plant” is shortsighted and dangerous.

Writing for the HuffPost, Nick Wing questioned the reliability of the FDA’s conclusions on kratom-related deaths. He stated that almost all the FDA cases involved subjects using multiple substances at the time of death, “with the vast majority including either illicit or prescription drugs that carry well-known fatal risks.” He concluded when taken together, the case reports fail to provide a clear picture of the deadly risks claimed by the agency with kratom. He gave examples from FDA case studies to illustrate his conclusions, but there was not a link in his article or the FDA press release to the case reports. And the given link in the FDA press release did not connect to the reports of the “36 deaths.”

Wing commented on the irony that many of the deaths the FDA associates with kratom also involved prescription drugs. But that seems to be part of the FDA concern, since “kratom has a strong bind to mu-opioid receptors,” meaning that when used in conjunction with other drugs, the combined adverse effects could be serious and even fatal.

Wing also said: “most of the emerging science on kratom has found it to be largely benign, especially when taken in low or moderate doses.” Andrew Kruegel, a chemist who has authored a number of studies on kratom, thought it was better to say kratom is an “atypical opioid,” given the differences between kratom and classical opioids. Kratom used alone may be less likely to lead to adverse events, but consumers need to be aware that it is an opioid. Even if it does have a better side-effect profile than classical opioids, the potential for adverse events when it’s mixed with other drugs seems to be a clear danger.

There was an FDA report, “CAERS: Kratom Deaths,” released on December 13, 2017. The case reports corresponding to the examples given in the HuffPost article could not be readily identified. But you can review the CAERS report for several examples of the dangers of kratom’s primary opioid agonist, mitragynine. Here are a few examples.

The cause of an accidental death for case # 10698706 was: mixed drug toxicity primarily mitragynine. “Despite the detection of the other compounds at therapeutic concentrations, they were considered to have additive toxic central nervous system effects in the presence of mitragynine and were therefore felt to have contributed toward the death.”

Case # 10708286 was a 17 year-old male who was self-medicating with kratom to treat a history of heroin abuse and chronic back pain. No other compelling cause of death beside mitragynine was evident. He had “a well-established history of opioid abuse, including Kratom abuse.” Kratom was present at the scene “and the active compound of this substance was identified in the decedent’s blood. Other drugs found were not felt to be significantly related to death.”

Case # 12569892 was a middle-aged man with a history of substance abuse and psychiatric problems for which he was taking medication, including Celexa, Lamictal, and zopiclone. He was being drug tested at work, so in order to avoid testing positive for a mind altering substance, he ordered kratom from the internet. He commented that his most recent batch seemed more potent than what he had previously. The concentrations of his prescription medications were within therapeutic levels and were felt to be of little significance in causing his death. There was a high concentration of mitragynine in his blood. “Mitragynine intoxication was assumed to be the main cause of death.” However, it could be that the other medications present may have enhanced the effects of the mitragynine.

When it’s used as a dietary supplement, kratom is considered to be a new dietary ingredient by the FDA. Dietary supplements typically require a New Dietary Ingredient Notification indicating the product is reasonably expected to be safe. “To date, the FDA is not aware of any evidence of safety establishing that kratom (or any compounds derived from kratom) will reasonably be expected to be safe as a dietary ingredient.” Some individuals use it to treat pain or other medical conditions, but there are no FDA-approved therapeutic uses of kratom, while there is evidence of significant safety issues. “Before it can be legally marketed for therapeutic uses in the U.S., kratom’s risks and benefits must be evaluated as part of the regulatory process for drugs established by Congress.”

Some individuals use it to treat their opioid dependency. But again, there is no reliable evidence to support kratom’s effectiveness for this use.

The CDC announced on February 20, 2018 that it was investigating a multistate outbreak of Salmonella infections. “Epidemiologic evidence indicates that kratom is a likely source of this multistate outbreak.” Eight of 11 people interviewed reported consuming kratom. There were no common brands, or suppliers identified at the time of the announcement. “At this time, CDC recommends that people not consume kratom in any form. The investigation indicates that kratom products could be contaminated with Salmonella and could make people sick.” The investigation is ongoing and will be updated as more information becomes available.

This outbreak associated with kratom-containing capsules, teas and powders, underscores the risk that harmful bacteria may contaminate these products when not subjected to manufacturing controls to eliminate that risk, in addition to the overall safety concerns for kratom itself.

In a February 21, 2018 FDA News Release, the agency announced the voluntary destruction and recall of a large volume of kratom-containing products manufactured and distributed by Divinity Products Distribution of Grain Valley Missouri under the names: “Botany Bay, Enhance Your Life and Divinity.” The company has also agreed to stop selling all products containing kratom. The FDA encouraged all companies involved in the sale of products containing kratom for human consumption to take similar steps to take their products off the market. FDA Commissioner, Scott Gottlieb said that some individuals use kratom believing it can help them treat their opioid dependency, “but there’s no reliable evidence to support kratom’s effectiveness for this use.” He added:

To protect the public health, we’ll continue to affirm the risks associated with kratom, warn consumers against its use and take aggressive enforcement action against kratom-containing products. We appreciate the cooperation of companies currently marketing any kratom product for human consumption to take swift action to remove these products from circulation to protect the public.

Kratom then is an unregulated substance with 23 compounds that qualify as opioids—atypical opioids if you prefer. In high enough doses it can be abused and lead to all the adverse effects common with opioids—withdrawal, cravings, anxiety, sleep disturbance, etc.  In combination with other substances it can lead to overdose and death. Marketed and sold as a dietary supplement for human consumption, it varies in strength with no real way for consumers to know the strength of what they are ingesting. Sounds like something the FDA would want to regulate.

For more on kratom, see: “The Secret of Kratom,” “Kratom: Part of the Problem or a Solution?” or “What is the Future of Kratom?”

02/2/18

Rebirth of the Gateway Hypothesis

© Lightsource | stockfresh.com

Writing for the journal Substance Use & Misuse in 2015, John Kleinig thought it was time to “retire” the gateway drug theory. The problem as he saw it was “there are too many gateways and ways of going through them, and we do not have an adequate handle on them.” He thought some versions of the hypothesis used an oversimplification of the dynamics of drug use and “developed [it] into a Medusa’s head of hypotheses about progressive drug use.”  The perceived risk leads to the development of  “social policies that prevent the downward passage through a gate or successive gates.”

The term gateway drug was popularized by Robert DuPont in his 1984 book, Getting Tough on Gateway Drugs: A Guide for the Family. DuPont had been the first director of NIDA (National Institute on Drug Abuse) from 1973-1978 and the second drug czar under Presidents Nixon and Ford from 1973 -1977. DuPont was said to have formed the idea of a gateway drug from two observations. First, some young people he came into clinical contact with reported they first used alcohol and tobacco, which was then followed by marijuana use. Second, because marijuana use was illegal, it was more likely other illegal drugs would be tried afterwards. His thesis was primarily used to demonize marijuana as the gateway drug.

DuPont did not, according to Kleinig, take the point of view that the pharmacological properties of some drugs could transport people through gateways. But others did, as we shall see.

If that had been intended, it would have provided a testable (albeit complex) scientific hypothesis and also provided valuable knowledge. It would have provided the kind of testable hypothesis that we have for some addictions—accounts of how, under certain conditions, particular psychoactive substances affect the chemistry and physiology of the brain, and so forth.

Kleinig seems to have been right in naming DuPont as popularizing the term gateway drug. But historically, the origins of the concept itself it should be attributed to Denise Kandel and her 1975 article for the journal Science, “Stages in Adolescent Involvement in Drug Use.” She initially theorized a four stage sequence to drug involvement: beer or wine or both; followed by cigarettes or hard liquor; marijuana; and other illicit drugs. “The legal drugs are necessary intermediates between nonuse and marihuana.”

Over the intervening years Kandel persevered with her hypothesis while others like Kleinig thought it should be abandoned. And she recently coauthored an article with her Nobel Prize winning husband that suggested pharmacological properties of some drugs could transport rats, if not people, through gateways. But I’m getting ahead of myself. Dr. Kandel edited Stages and Pathways of Drug Involvement: Examining the Gateway Hypothesis in 2002. In her introductory essay, “Examining the Gateway Hypothesis,” she acknowledged that while the “Gateway Hypothesis” originated in the mid-1970s, the idea of progression in drug use dates back to the 1930s as the “Stepping Stone Theory.”

She said there was a crucial difference between the two concepts. The Stepping Stone Theory saw the progression in drug involvement to be inevitable, “the use of marijuana invariably leading to heroin addiction.”  Recall that the 1930s was the time of films like: “Reefer Madness” and “Cocaine Fiends.” See “Remembering Reefer Madness” for more on this topic.

In contrast, the Gateway Hypothesis sees a sequence, where the use of certain drugs precedes the use of other classes, but that progression is not inevitable.  Entry into a particular stage may be common and perhaps even a necessary step, but is not a sufficient prerequisite to enter the next higher stage. Notice the modification below in her drug sequencing stages for the 2002 essay.

According to this notion, there is a progressive and hierarchical sequence of stages of drug use that begins with tobacco or alcohol, two classes of drugs that are legal, and proceeds to marijuana, and from marijuana to other illicit drugs, such as cocaine, metamphetamines, and heroin. The basic premise of the developmental stage hypothesis is that involvement in various classes of drugs is not opportunistic but follows definite pathways; an individual who participates in one drug behavior is at risk of progressing to another. The notion of developmental stages in drug behavior does not imply, however, that these stages are either obligatory or universal, nor that all persons must progress through each in turn.

Dr. Kandel pointed out that numerous investigations have documented regular sequences of progression from legal to illegal drugs among adolescents and young adults of both sexes, regardless of the age of their first use, ethnicity and country. The sequence has been observed in France, Israel, Australia, Japan, Spain and Scotland. She also noted there has been a resurgence of interest in the Gateway Hypothesis “as a framework for understanding adolescent drug involvement.”

An interview Dr. Kandel did with the NPR program, “All Things Considered” in 2015 indicated she had received a grant from NIDA in the early 1970s to study marijuana as a possible gateway drug. On her own initiative, she added questions about tobacco and alcohol use in order to look at other factors besides marijuana. Incidentally, this was during Dr. DuPont’s time as the NIDA director.

When I did the analysis, I found that there was a certain sequence that young people seem to be following when they got involved in drugs. They did not start with marijuana, but they started with drugs that are legal for adults in the society, such as beer and wine and cigarettes, other forms of alcohol.

Nearly forty years after her 1975 paper, she coauthored a paper for the New England Medical Journal with her husband, a Nobel Prize winning neuroscientist, “A Molecular Basis for Nicotine as a Gateway Drug.” “What we found is that when an animal was primed by nicotine and then was exposed to cocaine, the effect of cocaine was amplified many times.” Given how well nicotine primes the brain, she’s concerned about reports showing e-cigarette use is increasing among young people.

Although e-cigarettes eliminate some of the morbidity associated with combustible tobacco, they and related products are pure nicotine-delivery devices. They have the same effects on the brain as those reported here for nicotine … and they pose the same risk of addiction to other drugs and experiences.

The Kandels’ work was done in collaboration with Amir Levine and others; and it drew upon the earlier study by Levine et al., which also found how nicotine acted as a gateway drug on the brain. The effect “is likely also to occur when nicotine exposure is from passive and non-smoked forms.” The authors said this emphasizes the need to develop more effective public health prevention programs for all products containing nicotine, which would include e-cigarettes.

In November 2017 Griffin et al. published a study in Science Advances that showed a similar response with alcohol and cocaine. Alcohol was found to enhance cocaine addiction by suppressing two genes that normally inhibited the effects of cocaine, but not the other way around. In addition, their findings suggested that alcohol and nicotine acted through similar molecular mechanisms to increase vulnerability to cocaine. In other words, the use of one or the other gateway drug changed the brain in such a way that using cocaine was more rewarding.

Our findings indicate that a prior history of alcohol use is required for the enhancement of cocaine addiction–like behavior, and that priming by alcohol is a metaplastic effect, whereby exposure to this gateway drug initiates intracellular events that alter the epigenome, creating a permissive environment for cocaine-induced learning and memory, thereby enhancing the addictive potential of cocaine.

The New York Times published an article on the gateway drug theory, “A Comeback for the Gateway Drug Theory?” But it seemed to confuse Kandel’s Gateway Hypothesis and the Stepping Stone Theory without making the crucial distinction between them, as noted above. The Stepping Stone Theory is not an earlier version of the Gateway Hypothesis. Further misunderstanding was apparent in the criticisms of the Gateway Hypothesis the article cited.

The NYT article seemed to assume a version of the hypothesis that infers causation. It quoted an excerpt from a longer quote by Maia Szalavitz in her 2010 Time article on marijuana as a gateway drug. The excerpt in the NYT article was: “there is no conclusive evidence that the drug effects of marijuana are causally linked to the subsequent abuse of other illicit drugs.” Szalavitz was quoting from a report by the Institute of Medicine of the National Academy of Sciences. Below is the NYT quote from her article in context:

In the sense that marijuana use typically precedes rather than follows initiation of other illicit drug use, it is indeed a “gateway” drug. But because underage smoking and alcohol use typically precede marijuana use, marijuana is not the most common, and is rarely the first, “gateway” to illicit drug use. There is no conclusive evidence that the drug effects of marijuana are causally linked to the subsequent abuse of other illicit drugs.

Kandel’s essay, which is linked above, was careful to note the association, not causation inherent in the Gateway Hypothesis. She said the validity of the Gateway Hypothesis was based on two criteria: the sequencing of drug use between classes and the association of drugs, such that using a drug lower in the sequence increases the risk of using drugs higher in the sequence. “Ultimately, association implies causation if all possibilities for spurious associations have been eliminated. Given the difficulties of establishing true causality in the social sciences, the term association rather than causation is emphasized.”

Some of the other criticisms were not even on point to what Dr. Kandel was saying. A critic of the Gateway Hypothesis quoted in the NYT article was Ethan Nadelmann, the founder and former executive director of the Drug Policy Alliance. He said given that the study was on rats, to make claims about people from it was a stretch. Did this guy even look at the title of the Kandel and Kandel paper, “A Molecular Basis for Nicotine as a Gateway Drug,” let alone read it?

He also noted previous studies showing how one drug enhances the effect of another contradicted “gateway theory.” But again, that wasn’t relevant to Kandel’s Gateway Hypothesis. Nadelmann also alluded to research showing how individuals combining marijuana and prescription opioids were not more likely to abuse alcohol or other drugs.

Given the interest of Dr. Kandel in applying her research conclusions to public health concerns and policy issues, Dr. Nadelmann’s criticisms seem aimed at redirecting the attention of politicians like Jeff Session and Chris Christie and others away from seriously considering her research in the context of social and legislation reform of existing drug policy. The Drug Policy Alliance is a non-profit organization whose stated priorities include the decriminalization of responsible drug use. There seems to be dueling political ideologies at work here that either embrace or reject the Gateway Hypothesis.

Some serious political sparks may begin flying over Kandel and the Gateway Hypothesis soon. Dr. Kandel is wrapping up a similar study to those mentioned here on marijuana and hopes it will be ready for publication sometime in the first half of 2018. Given the careful science of Kandel and Kandel, the political firefights could get ugly if it demonstrates a molecular gateway for marijuana as the above studies have for nicotine and cocaine. But we’ll have to wait and see what they found and then concluded from their data. Pro marijuana legalization activists are probably wishing the Gateway Hypothesis had just remained dead.

11/17/17

Evolutionary Wars

credit: Steve Cardino, from “The Lie: Evolution”

The cartoon image here portrays a war between Humanism and Christianity, where Humanism is founded on evolution and Satan, while Christianity is founded on creation and Christ. The castle of Christianity is starting to collapse as the castle of Humanism systematically attacks the rock of its foundation in the cartoon, creation. The Christian guns are ineffectively aimed either nowhere or at the balloons (issues) of humanism instead of it evolutionary foundation. The message it sends is clear: Christianity is in danger of losing the cultural war with Humanism because it isn’t attacking the Satanic foundation it’s based on, evolution.

The cartoon originally appeared in a 1987 book by Ken Ham titled: The Lie: Evolution. In “Creation, Culture Wars, and the Search for Certainty,” Ted Davis said it has been the “signature icon” for Answers in Genesis (AiG), an organization founded by Ken Ham. Over time the image has been modified, as it reflected the ‘evolution’ of Ham’s and AiG’s thought. “Over time, I began to emphasize that believing in the creation account in Genesis means accepting God’s Word as the ultimate authority, and believing in the secular idea of evolution is to accept man’s word as the ultimate authority.”

In a 2002 version of the cartoon, the castle of Christianity was represented as being founded on six literal creation days equaling God’s authority, versus the millions of years equally man’s authority for the foundation of the humanism castle. In 2010, the foundations were “no longer creation vs. evolution or six days vs. millions of years, but ‘autonomous human reasoning”’ vs. ‘revelation/God’s word.’” See “Creation and Culture Wars” for the images.

Although Ham’s signature icon is still very much alive, it has evolved into a more sophisticated new species that is better adapted to twenty-first century culture wars, in which biblical faith is increasingly seen as contrary to science and reason. Ironically, Ham’s ministry itself is a primary cause of that perception.

Ted Davis noted how Ken Ham echoes the belief of William Jennings Bryan in the early twentieth century, that evolution inevitably undermines Christian faith. Like Ham, Bryan represented his thought in a cartoon. He saw evolution as causing modernism and leading to “the progressive elimination of the vital truths of the bible.” Bryan’s cartoon has three modernists, a student, a minister and a scientist descending a staircase that represents a slippery slope stemming from “the progressive elimination of the vital truths of the bible.” The descent starts with evolution and ends with the scientist stepping from Agnosticism to Atheism.

credit: original cartoon by Ernest James Pace; photograph by Ted Davis

The “Descent of the Modernists” cartoon appeared originally in Bryan’s 1924 book, Seven Questions in Dispute, published the year before his death, which took place days after his participation in the infamous Scope Trial. See “’Conflict Between Science and Religion’” and “No Contest; No Victory” for more on Bryan.

Despite the parallels in their thinking about creationism and the culture, Davis noted that Henry Morris, not Bryan, had the greater influence on Ham’s thought. AiG refers to the late Henry Morris as ‘the father’ of the modern creationist movement. His book, The Genesis Flood (1961), was the beginning of the revival of creationist thought that faded from the church with the passing of Bryan and the retreat of fundamentalism from cultural engagement after the Scopes Trial. Davis noted that in another book by Morris, The Troubled Waters of Evolution (1974), he argued evolutionary thought could be traced back beyond the “evolutionary pantheists” of the ancient Greco-Roman world. True as far as that statement goes, Davis noted where “Darwin’s theory was immensely more sophisticated and far more plausible than any ancient theory—but Morris goes much further.”

Morris traced the origins of evolutionary thought back through all the religions of the world other than Christianity, Judaism and Islam. These are excluded because they are based on Genesis. All other religions are “evolutionary” religions, including: Buddhism, Hinduism, Taoism, Confucianism, Atheism and ‘liberal Christianity.’ He said that evolution itself is a religion. He does not mean Darwinian evolution, but belief in the idea that all things have arisen by innate processes in the universe: the belief that the universe had no beginning; that it is eternal. You can watch a YouTube video series of a talk Morris gave titled “The Troubled Waters of Evolution.” It is in five parts. If you watch Part 1, notice the parallels between the metaphor Morris uses of the “fruit tree” of evolution producing harmful philosophies and evil practices the humanistic “balloons” in Ken Ham’s cartoon.

But Morris goes back even further in his book, The Troubled Waters of Evolution, according to Davis. He attributes the origins of evolution with Nimrod and the Tower of Babel in Genesis 10:8-10. According to Morris, it was part of the pantheistic polytheism of Babel Connected with astrology, idolatry, and the worship of fallen angels. “It is therefore a reasonable deduction, even though hardly capable of proof, that the entire monstrous complex [of evolution] was revealed to Nimrod at Babel by demonic influences, perhaps by Satan himself.” Therefore, evolution is “the world-view with which the whole world has been deceived.”

That’s why the foundation of Ham’s humanism castle connects evolution with Satan—and why evolution gets blamed for social ills that plagued us long before Darwin was born and would still be prevalent today even if Darwin had never existed. Evolution becomes the scapegoat for many sinful behaviors, to such an extent that it is virtually equated with sin itself, or even seen as inherently Satanic. This is a profoundly unhelpful way of approaching historical and cultural aspects of evolution, and it fails entirely to explain why many people who utterly reject evolution commit the very sins that Ham connects with belief in evolution.

Despite the revisions over time to the AiG “signature icon,” its foundations have actually changed very little. For AiG, Christianity sits on the foundation of “Creation;” which means “6  (24 hour) Days” for creation is equivalent to God’s authority; and only this interpretation is true “Revelation in God’s Word.” On the other hand, Humanism sits on the foundation of “Evolution;” which wrongly believes in “millions of years” for creation according to human authority; making “human reason autonomous” from the revelation of God’s Word. In other words, respect for the authority of God’s Word requires an agreement with the AiG view of creation in six 24 hour days—and its companion doctrines of 6,000 years since the creation and a global Noachian Flood (See the AiG Statement of Faith). In contrast, Humanism and its issues rest on autonomous reason, manifested in allowing millions of years for creation and allowing evolution rather than creation to explain how the universe and humanity came into being.

Lastly, the warfare metaphor in the AiG “signature icon” was actually first used by John William Draper and Andrew Dickinson White in their books on the perceived conflict or “war” between science and religion at the end of the 19th century. Draper wrote History of the Conflict Between Religion and Science (1874) and White wrote History of the Warfare of Science with Theology in Christendom (1896). In the Preface of his book, Draper seemed to set conflict between religion and science on a foundation that was eerily similar to the 2010 AiG cartoon. “The history of Science is … a narrative of the conflict of two contending powers, the expansive force of the human intellect on one side, and the compression arising from traditionary faith and human interests on the other.”

Warfare or conflict rhetoric tempts us to see dichotomy where there may not be one. And when Christians use it to compare their understanding of a Biblical passage like Genesis 1 to alternative interpretations by other Christians (who also affirm the authority of Scripture), they need to be aware of the danger of imputing the rightful authority of Scripture onto their interpretation of the Biblical passage in question. It seems to me that is what has happened with Henry Morris and AiG.

02/24/17

Misdiagnosing Substance Use

© adiruch | 123rf.com

Allen Frances doesn’t like the DSM-5 and you can hear him say so here.  He said our mental health system was in a mess. And he is afraid that with DSM-5, it will get even worse. “People who are essentially normal are being diagnosed with mental disorders they don’t have.” Small changes in the diagnostic system can result in tens of millions of normal people qualifying for a diagnosis. He used himself as an example, stating how he would qualify for several of the DSM-5 disorders. Typical symptoms of grief over his wife’s death, lasting beyond two weeks, would have signified him as having a Major Depressive Disorder.

Anther mistake was combining what had been two different diagnoses of substance use in the DSM-IV—Substance Abuse and Substance Dependence—into one: Substance Use Disorder. Substance Abuse was when someone had recurrent, but intermittent, trouble from recreational binges. Substance Dependence was a continuous and compulsive pattern of use, often with tolerance and withdrawal. The majority of substance abusers “never become addicted in any meaningful sense.”

The two DSM IV diagnoses have radically different implications for treatment planning and for prognosis. Artificially lumping them together in DSM-5 forces inaccurate diagnosis, loses critical clinical information, and stigmatizes as addicts, people whose substance problem is often temporary and influenced by contextual and developmental factors.

Hasin et al., “DSM-5 Criteria for Substance Use Disorders: Recommendations and Rationale,” presents the rationale used by the DSM-5 workgroup for substance use disorders for its changes, particularly combining abuse and dependence into one disorder. They recommended the combination as well as dropping one diagnostic criteria (legal problems) and adding one (craving). Two criteria are required to diagnose a Substance Use Disorder. The number of criteria met will indicate mild (2 to 3 criteria), moderate (4 to 5), and severe disorders (6 or more). The following chart, taken from the article, illustrates the changes from DSM-IV to DSM-5.

Frances is not alone in seeing value with two distinct types of substance use disorder. Carleton Erickson in The Science of Addiction noted how the distinction allowed for the differentiation between individuals with drug-related problems who could stop using when they wished (substance abusers), and others who had the disease of chemical dependence. Chemically dependent people have a dysregulation of the mesolimbic dopamine system and generally cannot stop using drugs without intensive intervention into their drug use problems. “According to these criteria, drug abuse in intentional, ‘conscious,’ or voluntary. Drug dependence is pathological and unintended.”

In his article, “DSM-5 Made a Mistake Eliminating Substance Abuse,” Allen Frances indicated the DSM-5 workgroup for substance use disorders based its rationale for dropping Substance Abuse on studies suggesting the distinction was hard to make. He said the results of the studies were not definitive. Moreover, their interpretation was flawed by what he said was a basic DSM-5 misunderstanding of the nature of psychiatric diagnosis. “All DSM disorder overlap with other DSM disorders and also frequently with normality.” Fuzzy boundaries among near diagnostic neighbors are common and not a sufficient excuse to collapse clinically valuable distinctions.

Carleton Erickson’s discussion of the degrees of severity with drug problems helps to illustrate this misunderstanding. He indicated there were mild, moderate and severe forms of both drug abuse and drug dependence. Most people don’t think in terms of severity with substance use problems. You either have a problem or you don’t; you either abuse drugs or you don’t. He then illustrated their relationship to drug-seeking behavior as follows.

Drug Abuse

Drug Dependence

Drug-Seeking

Mild

Little/None

Moderate

Some

Severe

Mild

A Lot

Moderate

Even more

Severe

All the Time

The overlap referred to by Frances occurs between severe drug abuse and mild drug dependence. The inability of psychiatric diagnosis to make a clear distinction here seems to have led to the decision to collapse the abuse and dependence diagnoses into one category in the DSM-5.

I think another overlap between drug abuse and drug dependence happens with regards to self-control. A distinction is necessary between self-control of thoughts, feelings and behavior when drinking and control of the drug intake itself. Any substance use can lead to a loss of self-control over an individual’s thoughts, feelings and behavior. When that loss of control results in recurrent, intermittent trouble, there is a drug abuse problem. The severity of this type of loss of self-control and the related intermittent trouble varies.

Not everyone who abuses a drug experiences the classic sense of losing of control over how much of the drug they use. A loss of control over drug intake—a continuous and compulsive pattern of use—is only evident within drug dependence. And again, the severity of this loss of control over drug intake varies. So I’d adopt Erickson’s degrees of severity with drug abuse and dependence problems as seen below.

Loss of Self-Control in Abuse

Loss of Control over Drug Intake in Dependence

Mild

Moderate

Severe

Mild

Moderate

Severe

A substance abuse problem with severe trouble related to loss of self-control may be indistinguishable from a substance dependence problem with mild loss of control over drug intake. Both people would look at their severe “trouble” and attribute it to drinking or drugging too much. Given an equal motivation to avoid further “trouble,” the substance abuser would likely have an easier time maintaining abstinence. Carleton Erickson said chemical dependence is not a “too much, too often, withdrawal” disease; it’s a “I can’t stop without help disease.” There is a pathological, compulsive pattern to substance use.

There does seem to be a “fuzzy boundary” between Substance Abuse and Substance Dependence. Nevertheless, the distinction still carries some clinical and diagnostic value. I agree with what Allen Frances said: “The change was radical, creates obvious harms, and provides no apparent benefit.” What should clinicians do? Frances suggested they simply ignore the DSM-5 change. He said it was appropriate and clinically preferable to continue making the distinction.

There is nothing sacred or official about the DSM-5 choices — I know because I made the choices for DSM-IV. The ICD coding system is official; the DSM codes are just one groups’ fallible adaptation of them. It is of great significance that the official coding in ICD-10-CM does not follow the DSM-5 decision to eliminate Substance Abuse. Instead, ICD-10-CM retains the DSM-IV terminology and continues to provide separate Substance Abuse and Substance Dependence codes for each of the major classes of substances.

The ICD-11 workgroup, currently in the final stage of development before field tests, will continue to separate Substance Dependence and Harmful Substance Use. The guidelines for dependence are revised and simplified into three diagnostic features: impaired control over substance use; increasing priority in life and physiological features. Severity qualifiers were suggested only for alcohol intoxication. They also introduced a new diagnostic category, with no equivalents in ICD-10 or DSM-5: single episode of harmful use. Frances commented:

The DSM-5 mistake thus places it out of line with ICD-10, ICD-11, previous DSM’s, and well established clinical practice. Clinicians remain truer both to clinical reality and to ICD coding when they ignore the new DSM-5 lumping of substance use disorders and instead continue to distinguish Substance Abuse from Substance Dependence. DSM’s are explicitly meant to be used only as guides, not worshiped as bibles. Clinicians are free to ignore DSM whenever it makes mistakes that go against clinical common sense and the International coding system.

01/13/17

Iatrogenic Gun Violence

© StephanieFrey | stockfresh.comfresh eggs. Araucanas are also known as the Easter Chicken for the blue or greenish colored eggs they lay.

Whenever I read about horrific violence like the incident in the Fort Lauderdale airport, I wonder what role psychiatric medications played. I wonder if the violent behavior was iatrogenic—was it caused by psychiatric medications? This question will sound counter intuitive for many people. Surely the reverse is true. Psychiatric medication and proper diagnosis should have prevented it. Let’s see if it is.

Esteban Santiago was deployed to Iraq from April 2010 to February 2011 with the 130th Engineer Battalion, the 1013th Engineer Company of the Puerto Rico National Guard. After flying from Alaska to Fort Lauderdale Florida, he retrieved his baggage, which incidentally contained a semi-automatic handgun. Santiago had followed proper protocol, checking the weapon with TSA. He went into the men’s bathroom, loaded his weapon and opened fire in Terminal 2 of the airport, killing five people and wounding six others. A witness said he was just randomly shooting people, with no rhyme or reason to it.

Family members reported that he was a changed man when he returned from Iraq. His aunt said his mind was not right. At times he seemed normal, but other times he seemed lost. In Iraq, his unit cleared roads of improvised explosive devices and maintained bridges. Two people in his unit died while he was in Iraq. His aunt said: “He talked about all the destruction and the killing of children. He had visions all the time.” He had changed.

His brother Bryan confirmed that recently Esteban was hallucinating, but said he was receiving psychological treatment. Bryan said he believes the shooting rampage resulted from mental issues that surfaced after the Iraq tour. When Esteban’s tour ended, he was hospitalized for mental problems. Upon his release, he went to Puerto Rico where his father was ill and eventually died. While in Puerto Rico, he received mental health therapy. Esteban eventually moved to Alaska, where he joined the Alaska National Guard in November 2014. He was discharged in August of 2016.

Over the course of 2016, Santiago was repeatedly reported to Anchorage police for physical disturbances. In January of 2016 he was arrested and charged with assault and criminal mischief after an argument with his girlfriend. He allegedly yelled at her while she was in the bathroom and broke down the bathroom door. She told investigators that he tried to strangle her and struck her on the side of the head.

Santiago pleaded no contest to criminal mischief and assault charges. Under a deferred prosecution agreement, his charges would have been dismissed if he complied with the conditions. He was due back in court on March 28th, 2017 to assess his progress.

While living in Alaska, Esteban continued to receive psychological treatment, according to his brother. Although his girlfriend alerted the family to the situation in Alaska, Bryan said he did not know what mental health problem Esteban was being treated for; they never spoke about it by phone.

His son was born in September of 2016. In November of 2016, Esteban walked into an FBI office in Anchorage to report that his mind was being controlled by a U.S. intelligence agency. He told officials he had a firearm in his car, along with his newborn son. Santiago was checked into a mental health facility; his firearm was logged as evidence for safe keeping. The infant’s mother came for their child. FBI special agent Marlin Ritzman said:

During the interview, Mr. Santiago appeared agitated, incoherent and made disjointed statements. Although he stated he did not wish to harm anyone, as a result of his erratic behavior our agents contacted local authorities, who took custody of Mr. Santiago and transported him to the local medical facility for evaluation.

After conducting database reviews, interagency checks and interviews with his family members, the FBI closed its assessment of Santiago. Agents found no ties to terrorism during their investigation. A CNN senior law enforcement analyst and former FBI assistant director said Santiago hadn’t been adjudicated a felon and he hadn’t been adjudicated as mentally ill. So they couldn’t keep his weapon. The Walther 9-millimeter pistol was returned to him in the beginning of December. Authorities told CNN it was the pistol he used in the shooting incident in Fort Lauderdale.

Typically, Esteban was considered to be a calm young man who was never violent. Recently he began selling his possessions, including his car. Friends and associates noticed more erratic behavior. He bought a one-way ticket to Fort Lauderdale and packed his pistol and two magazines. His carryon bag with the pistol was his only luggage. He flew from Anchorage to Minneapolis to Fort Lauderdale. He retrieved his bag from the baggage claim area and went into a men’s room stall to load his pistol.

He shot the first people he saw, going up and down the carousels of the baggage claim, shooting through luggage to get at people that were hiding. He thinks he fired 15 bullets, aiming at his victim’s heads. A witness said Esteban showed no remorse. He didn’t say anything. “No emotion, no nothing. About as straight-faced as you get.” Afterwards, he just lay face down, spread eagle, waiting for the deputies to come and get him.

The above report was pieced together from information contained in the following reports by The New York Times here,  NJ.com here, CNN here, and NPR here.

There was no explicit mention of Santiago’s repeated involvement in “psychological treatment” involving psychiatric medications, but it highly probable he was taking psychiatric medication of some sort. The lack of any mention of his being prescribed medication may simply be due to confidentiality regulations. Or this silence could be due to the chicken-and-egg argument often applied to incidents involving violence and individuals with known psychiatric problems. Their mental illness, not the drugs to treat it, caused their horrific behavior.

Several psychiatrists have voiced concerns with psychiatry, its over reliance upon medication and denial of serious adverse effects from medication, like violence and suicide. Joanna Moncrieff said she’s sad her profession has not taken the harms drug treatments can do more seriously. She said it has a long history of ignoring the adverse effects of drugs, or attributing them to the underlying disease—of blaming the patient instead of the drug. “Too many psychiatrists have just accepted that drug treatments are good, and have not wanted to contemplate that actually these treatments could be harmful.”

First and foremost, she said, psychiatry needs to adopt a drug-centered model for understanding its drug treatments and what they do to people. Psychiatrists need more information, knowledge and training on what the drugs do—what effects they produce in people; “how they change the way that people think and feel and what sort of impact those changes have on people’s lives.” Watch two brief videos of her expressing her concerns here. You can read more about her “drug-centered model” here on this website: “A Drug is a Drug is a Drug.”

Peter Breggin has raised concerns with the association of violence and antidepressants since the early days of Prozac. In his 1991 book, Toxic Psychiatry, Dr. Breggin related newspaper and scientific reports pointing to an association between Prozac and “compulsive, self-destructive and murderous activities.” He said then he was personally familiar with several cases of compulsive suicidal or violent feelings that developed after taking Prozac. Over the years, his familiarity grew.

In “Psychiatry Has No Answer to Gun Massacres,” Breggin described how the Columbine High School shooter, Eric Harris had a “therapeutic” level of Luvox (fluvoxamine) in his body at the time of the murders.  He had a dose increase in his medication 2 ½ months before the assault and showed signs of drug toxicity five weeks before the event. James Holmes, the Aurora Colorado theater shooter, was in psychiatric treatment with the medical director of student health services, who was considered an expert on campus violence. She was concerned enough about Holmes to report him to the campus police and the campus threat assessment team a few weeks before the assault. When the assessment team suggested putting him on a 72-hour involuntary hold, she rejected the idea. “When Holmes quit school, the school washed its hands of all responsibility for him.”

In a 2010 journal article, “Antidepressant-Induced Suicide, Violence, and Mania: Risks for Military Personnel,” Dr. Breggin related how the adverse effects described in the 2009 edition of the Physicians’ Desk Reference for Zoloft (sertaline) resembled the most frequent psychiatric disorder associated with combat—PTSD—with its hyperalert overstimulated symptoms. He said identical or nearly identical warnings can be found in all antidepressant labels. “All these potentially dangerous symptoms are also commonly seen in PTSD in military personnel, posing the risk of worsening this common military disorder.”

Looking at the revised 2016 medication guide for Zoloft, we see that nothing much has changed with regard to adverse effect warnings. It said Zoloft and other antidepressant medications could increase suicidal thoughts or actions. Symptoms needing immediate attention included: acting aggressively or violent, feeling agitated, restless angry or irritable, an increase in activity or talking more than what is normal, acting on dangerous impulses, trouble sleeping, new or worse anxiety or panic attacks, trouble sleeping, other unusual changes in behavior or mood.

A condition known as “serotonin syndrome” has symptoms such as: agitation, hallucinations, coma and other changes in mental status. Symptoms of potential manic episodes included: greatly increased energy, racing thoughts, unusually grand ideas, severe trouble sleeping’s, reckless behavior, excessive happiness, talking more or faster.

Dr. Breggin concluded his article with the following cautions and recommendations. He said there was a strong possibility the increased suicide rates among active-duty soldiers were in part caused or made worse by the widespread prescription of antidepressant medication. Alone, they can cause a stimulant-like series of adverse effects. “These symptoms of activation can combine adversely with similar PTSD symptoms found so commonly in soldiers during and after combat.” He recommended the military study the relationship between psychiatric drug treatment and suicide as well as random or personal violence. He also suggested that antidepressants should be avoided in the treatment of military personnel.

Another emerging concern of an association between antidepressants and violence is in the research done by Yolande Lucire. She suggested that mutations in CYP450-encoding genes contributed to problems metabolizing psychiatric drugs, and thus were contributing factors in three cases of antidepressant-induced akathisia-induced homicide. The cytochrome P450 family of enzymes is responsible for metabolizing most of the drugs used in psychiatry. You can read her article here. You can also find another article: “Psych Drugs and Violence” on this web site. Within that article you will find a link to another article by Lucire on antidepressant-induced akathisia-related homicide and the CYP450 genes.

Hasn’t there been enough evidence associating suicide and violence with psychiatric medications, especially antidepressants, for open dialogue and more comprehensive scientific research into this public health issue? How many more Columbines, Auroras and Fort Lauderdales need to happen before we begin to address the association of psychiatric drugs and violence?

11/22/16

Antidepressant Misuse Disorder

54164089 - antidepressant pills 3d rendering isolated on white background

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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.”

10/18/16

Dancing with the Devil

© choreograph | stockfresh.com

© choreograph | stockfresh.com

I once knew a woman who had an anxiety disorder. She also abused benzodiazepines. She was able to conjure up a panic attack in a doctor’s office and walk out with a prescription for the benzo of her choice. At one time, she had four concurrent prescriptions for these anti-anxiety medications. Another person I know of has a ten-year history of using benzodiazepines at close to the maximum recommended dose. When he had an unexpected short-term hospital stay, the treating physicians were reluctant to continue prescribing benodiazepines at such a high level while he was in the hospital. When he returned home, in case his medical issue resulted in another unexpected stay, he put together an emergency hospital kit with various things—including extra benzodiazepines.

A study published in the American Journal of Public Health in April of 2016 found that benzodiazepines were the second most common drug in prescription overdose deaths for 2013. Given the common knowledge of the potential dangers of benzodiazepines and people becoming more aware of opioids, Marcus Bachhuber and a team of researchers thought that their study would show a steady of declining pattern for prescribing benzodiazepines. But they found exactly the opposite. Between 1999 and 2013 there was an increase of 30% among adult Americans who filled a benzodiazepine prescription. In addition, the amount of medication within a prescription doubled over the same time period.

Bachhuber was quoted by CNN as saying the study’s findings were very concerning. The risk of overdose and death from benzodiazepines alone is said to be generally lower in otherwise healthy adults. But in combination with other drugs like alcohol or opioids, they can be lethal.

Future research should examine the roles of these potential mechanisms to identify effective policy interventions to improve benzodiazepine safety. In particular, as underscored by several recent reports, interventions to reduce concurrent use of opioid analgesics or alcohol with benzodiazepines are needed.

The overdose problem with benzos has been overshadowed by the problems with prescription opioids. Writing for CNN, Carina Storrs said: “The current study could help shine a light on the problem of benzodiazepine abuse and overdose.” Dr. Gary Reisfield, a professor of psychiatry at the University of Florida, referred to the problem with benozdiazepines as a “shadow epidemic”:

Much attention has been paid to the explosion of prescription opioid prescribing and the associated morbidity and mortality. Much less attention has been paid to the shadow epidemic of benzodiazepine prescribing and its consequences.

A 2015 study by Jones and McAninch found that emergency department visits and overdose deaths involving opioids and benzodiazepines increased significantly between 2004 and 2011. Overdose deaths from combining the two classes of drugs rose each year from 18% in 2004 to 31% in 2011. This rate increased faster than the percentages of people filling prescriptions and the quantity of pills in the prescriptions.

As Dr. Indra Cidambi wrote in “Are We Ignoring an Escalating Benzodiazepine Epidemic?”,  she observed with increasing alarm the rising rate of concurrent use/abuse of benzos among opiate users. She pointed to two possible factors driving this trend. First, some opiate abusers use benzos to “spike” the euphoria from their opiates. Second, patients often receive their prescriptions from two different physicians. She said that it is “notoriously difficult” for doctors to refuse to prescribe these two medications.

Unfortunately, and ironically, pain and anxiety are neither verifiable nor quantifiable through medical testing! Consequently, self-reported symptoms by patients are the sole basis on which prescriptions for these medications are written, enabling individuals addicted to these medications to obtain them fairly easily.

Dr. Cidambi recommended the establishment of a national database for physicians to verify whether or not a patient has been prescribed one of these medications before prescribing or filling a prescription for the other. Second, she said physicians should develop limited, short-term treatment plans from the beginning to treat noncancerous pain with opiates and anxiety with benzodiazepines.

Studies have shown the decreasing efficacy of long-term treatment for pain with opioid medications, and evidence-based treatment protocols for benzodiazepines clearly indicate that long-term use of benzodiazepines is not recommended.

In “Benzos: A Dance with the Devil,” Psychiatrist Kelly Brogan described some of her work helping patients taper off of benzodiazepines. A woman who had been placed on Remeron (an antidepressant) and Klonopin (a benzodiazepine) for eight years said of her original prescriber: “He never once told me there might be an issue with taking these meds long-term. In fact, he told me I probably needed them after I tried stopping them cold turkey and felt so sick I thought I was dying.” Brogan said no one ever discussed with this woman or her patients the true risks, benefits and alternatives to psychiatric medications like benzodiazepines, “perhaps because we as clinicians are not told the full story in our training.”

She went on to quote from a paper by another psychiatrist, Peter Breggin, on the risks of benzodiazepines, which include: cognitive dysfunction that can range from short-term memory impairment and confusion to delirium; “disinhibition or loss of impulse control, with violence toward self or others, as well as agitation, psychosis, paranoia and depression.” There can also be severe withdrawal symptoms, ranging from anxiety and insomnia to psychosis and seizures after abruptly stopping long-term larger doses. The person can re-experience their pre-drug symptoms as they taper. These so-called rebound symptoms of anxiety, insomnia and others serious emotional reactions can be more intense than they were before drug treatment began. And don’t forget dependency or abuse.

Psychiatrist Allen Frances, the former chair of the DSM-IV, recently wrote: “Yes, Benzos Are Bad for You.” He introduced his article by saying that he was going to say some very negative things about benzodiazepines in the hope that doctors think twice before prescribing them and patients are discouraged from taking them. Benzos were wonder drugs in the 1960s. Anyone remember the 1966 song, “Mother’s Little Helper,” by the Rolling Stones? These drugs were reputed to be safe, and so were used for a variety of “ills,” such as anxiety, alcohol use disorders (yes, really), to take the edge off of agitation in dementia, and to help people sleep. “Initially we were pretty oblivious to the risk of addiction.” So benzodiazepines quickly became the most prescribed medications in America.

A second craze began in the 1980s with the release of Xanax. Frances said the dose to treat panic disorder was “dangerously close” to the dose leading to addiction. “This should have scared off everyone from using Xanax, but it didn’t.” It remains a best seller, with its own “brand” that now leads to fentanyl be pressed into counterfeit Xanax pills. See “Buyer Beware Drugs” and Paul Gaita’s article on fake Xanax laced with fentanyl.

The real wonder of the benzos is that sales continue to boom, despite their having so little utility and no push from pharma marketeering (because patents have run out – thereby decreasing costs and profits.) Between 1996 and 2013, the percentage of people in the U.S. using benzos jumped more than one-third from an already remarkable 4.1 to 5.6 percent. Especially troubling is that benzo use is ridiculously high (nearly one out of ten) in the elderly, the group most likely to be harmed by them.

Frances said the beneficial uses of benzodiazepines can be counted on the fingers of one hand: short-term agitation in psychosis, mania and depression; catatonia; “as needed” use for times of special stress, like fear of flying, or for sleep. While they should be used very short term, in real life most people take them long term—“in doses high enough to be addicting, and for the wrong reasons. . . . Benzos are very easy to get on, almost impossible to get off.”

In addition to the harm from overdoses, Frances described the painful and dangerous withdrawal symptoms, which he said are a “beast.” Common symptoms are irritability, insomnia, tremors, distractibility, sweating and confusion. “The anxiety and panic experienced by people stopping benzos is usually much worse than the anxiety and panic that initially led to their use.”  Concurrent use or abuse of alcohol or other drugs, like opioids, complicates withdrawal even further.

The most insidious issues with benzos for Frances, is how they effect brain functioning. Especially with the elderly, ongoing benzo use can be devastating. Many elderly begin their downward spiral to death and disability from falls—that happen from their benzo use! He said: “If you meet an elderly patient who seems dopey, confused, has memory loss, slurred speech, and poor balance, your first thought should be benzo side effects — not Alzheimer’s disease or dementia.” See “Sedating Seniors” for more information on this topic. It’s been over 30 years since he last prescribed a benzo for anxiety.

The tough question is what to recommend for those many unfortunates already suffering the tyranny of benzo addiction. Should they stay the course to avoid the rigors and risks of withdrawal or should they make the great effort to detox? This is an individual decision that can’t be forced on someone. But the longer you are on them, the harder it gets to stop, and the cognitive side effects of benzos create more and more dysfunction as your brain ages. The best bet is to stick with a determined effort to detox, however long and difficult, under close medical supervision. On a hopeful note, some of the happiest people I have known are those who have overcome their dependence on benzos.

So it was encouraging to see that the FDA will require class-wide changes in drug labeling to bring attention to the dangers of combining opioids and benzodiazepines. The changes will include boxed warnings on nearly 400 products with information on the risks of combining these medications. The FDA Commissioner, Robert Califf said: “It is nothing short of a public health crisis when you see a substantial increase of avoidable overdose and death related to two widely used drug classes being taken together.” He implored health care professionals to carefully and thoroughly evaluate on a patient-by-patient basis whether the benefits outweigh the risks when using these drug classes together.

Used alone or in conjunction with opiates, benzodiazepines are potentially lethal and addictive. A too sudden withdrawal from benzodiazepines can be fatal, where the same is rarely true with opiates. They work quickly and effectively for anxiety and sleep problems and yet they can have a multitude of side effects, including addiction. Did I say they are addictive? Using benzodiazepines has become a dance with the devil for too many unsuspecting individuals … those that are still alive to regret it, that is.

This article previously appeared on the addiction and recovery website “The Fix” under the title of “Dangerous Dance.”