02/23/18

Priming Young Adults with Vaping

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The National Institute of Health announced that recent national survey research discovered that almost 1 in 3 (27.8%) 12th graders reported some kind of use of a vaping device in the past year, while the use of hookahs and regular cigarettes is declining. When asked what they thought was in the mist they inhaled, 51.8% said it was just flavoring, 32.8% said the mist contained nicotine, and 11.1% said they were smoking marijuana or hash oil. Nora Volkow, the director of NIDA, said: “We are especially concerned because the survey shows that some of the teens using these devices are first-time nicotine users.” Recent research suggests some of them could move on to regular cigarette smoking … or other drugs. And some additional research suggests many teens don’t actually know what is in the device they are using.

Monitoring the Future (MTF) is a yearly survey of 8th, 10th and 12th graders in school nationwide. The MTF survey is done by the Institute for Social Research at the University of Michigan for NIDA, the National Institute on Drug Abuse. When the survey asked about vaping over the past month, 11% of 12th graders reported vaping nicotine and 4.9% reported vaping marijuana. See the following chart from the NIH news release.

According to the CDC, e-cigarettes are now the most commonly used form of tobacco by youth in the U.S. Dual use, using both regular cigarettes and e-cigarettes, is also common among young adults 18-25. The reasons reported by young people for trying e-cigarettes include curiosity, taste and the belief they are less harmful than other tobacco products. Over 80% of teens and young adults who use e-cigarettes said they use flavored e-cigarettes.

Back in June of 2016 the FDA finalized a rule that extended its regulatory authority to all tobacco products, including e-cigarettes, cigars, hookahs and pipe tobacco. The rule requires health warnings and bans free samples. It also restricts youth access to newly regulated tobacco products by not allowing their sale to those younger than 18 and requiring a photo ID. Manufacturers will have up to two years to continue selling their products while they submit a new tobacco product application (and an additional year while the FDA reviews the application).

The rule will help prevent young people from starting to use these products, help consumers better understand the risks of using these products, prohibit false and misleading product claims, and prevent new tobacco products from being marketed unless a manufacturer demonstrates that the products meet the relevant public health standard.

If the new technology in e-cigarettes helps reduce toxicity compared to conventional cigarettes, encourages current smokers to switch completely and/or are not widely used by youth, they potentially could reduce disease and death. “But if any product prompts young people to become addicted to nicotine, reduces a person’s interest in quitting cigarettes, and/or leads to long-term usage with other tobacco products, the public health impact could be negative.” The FDA encouraged manufacturers to explore product innovations that would maximize potential benefits and minimize risks. The revised rule allows the FDA to further evaluate the impact of these products on the health of both users and non-users.

Psychiatric Times reported e-cigarettes were first developed and commercialized in China in 2003. They entered the US market in 2006. During their first ten years on the market, before the FDA ruling discussed above, advertising and sales of e-cigarettes increased exponentially every year. “While tobacco advertising has been banned from television and radio since 1970, e-cigarettes are promoted widely on these media channels, on the web, and in social media, with many ads reaching youth.” Mislabeling has been a problem with some products labeled as nicotine-free containing nicotine and others having higher concentrations of nicotine than labeled.

The evidence for e-cigarettes as a cessation aid to quit regular cigarette smoking is limited. Dual use of regular cigarettes and e-cigarettes is common. One study reported half of current smokers report regular use of e-cigarettes. A meta-analysis of twenty controlled studies found the odds of quitting cigarettes was 28% lower in individuals who used e-cigarettes. However only 2 randomized controlled trials have been done, and: “The quality of evidence was judged to be low grade, and in both trials, e-cigarettes with nicotine were no different in efficacy for quitting smoking than placebo (nicotine-free) e-cigarettes.”

So at this point in time, the evidence does not support the use of e-cigarettes as an aid to stop smoking regular cigarettes. It should be noted that the American Heart Association’s policy statement of e-cigarettes does not recommend their use. However, if a patient has tried and failed other cessation methods or is unwilling to try them, the AHA does recommend trying e-cigarettes for smoking cessation.

There is evidence that smoking e-cigarettes increases the risk of cardio vascular problems. Swedish researchers, in Antoniewicz et al., demonstrated that in healthy volunteers, ten puffs from an e-cigarette caused an increase in endotheial progenitor cells (EPSs) of the same magnitude as smoking one traditional cigarette. The average e-cigarette user takes 230 puffs per day, raising the prospect that prolonged use could result in serious health consequences. “These findings suggest that a very short exposure to ECV [e-cigarette vapor] caused a rapid EPC mobilization in blood, which may indicate an impact on vascular integrity leading to future atherosclerosis [hardening of the arteries].” A heart specialist for the European Society of Cardiology was quoted in the Daily Mail as saying: “It really surprises me that so little vapour from an e-cigarette is needed to start the heart disease ball rolling. It’s worrying that one e-cigarette can trigger such a response.”

Researchers at the University of Connecticut found evidence that e-cigarettes containing a nicotine-based liquid are potentially as harmful as unfiltered cigarettes in causing DNA damage. The study’s lead author said the results surprised him. “I never expected the DNA damage from e-cigarettes to be equal to tobacco cigarettes.” He was shocked the first time he saw the result, so he diluted the samples and ran the controls again. “But the trend was still there – something in the e-cigarettes was definitely causing damage to the DNA.”

Researchers at the University of North Carolina found that not only do e-cigarettes trigger the same immune responses as regular cigarettes, they also trigger some unique reactions. E-cigarette users uniquely showed significant increases with neutrophil-extracellular-trap (NET)-related proteins in their airways. “Left unchecked neutrophils can contribute to inflammatory lung diseases, such as COPD and cystic fibrosis.” The study also found that e-cigarettes produced negative consequences known to occur in regular cigarettes such as an increase of biomarkers of oxidative stress and activation of defense mechanisms associated with lung disease. They also found an over secretion of mucus secretions that have been associated with diseases like chronic bronchitis, bronchiectasis and asthma.

Another study by Eric and Denise Kandel, “A Molecular Basis for Nicotine as a Gateway Drug” has raised concerns with e-cigarettes as “pure nicotine-delivery devices.” Their study demonstrated that nicotine acted like a gateway drug for cocaine on the brain of mice, “and this effect is likely to occur whether the exposure is from smoking tobacco, passive tobacco smoke, or e-cigarettes.”

These results provide a biologic basis and a molecular mechanism for the sequence of drug use observed in people. One drug affects the circuitry of the brain in a manner that potentiates the effects of a subsequent drug.Although the typical e-cigarette user has been described as a long-term smoker who is unable to stop smoking, the use of e-cigarettes is increasing exponentially among adolescents and young adults. Our society needs to be concerned about the effect of e-cigarettes on the brain, especially in young people, and the potential for creating a new generation of persons addicted to nicotine. The effects we found in adult mice are likely to be even stronger in adolescent animals. Priming with nicotine has been shown to lead to enhanced cocaine-induced locomotor activity and increased initial self-administration of cocaine among adolescent, but not adult, rats. Whether e-cigarettes will prove to be a gateway to the use of combustible cigarettes and illicit drugs is uncertain, but it is clearly a possibility.

Don’t be too quick to dismiss the Kandels’ nicotine-gateway theory. They were doing basic research on the effects of nicotine on specific areas of the brain. Priming with nicotine enhanced the effects of cocaine in the nucleus accumbens. “Priming with nicotine appeared to increase the rewarding properties of cocaine by further disinhibiting dopaminergic neurons in the ventral tegmental area.” They only observed the priming effect of nicotine when mice were given cocaine at the same time as nicotine. For more on Denise Kandel’s gateway hypothesis see: “Rebirth of the Gateway Hypothesis.”

02/20/18

The Birth of Christian Creeds

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In “Legend of the Apostles’ Creed,” I looked at the belief of how the Twelve Apostles agreed upon a standard for their future preaching that came to be known as the Apostles’ Creed. But this legend was just a “pious fiction.” However, there was evidence for “creeds of a looser sort,” lacking the textually determined state of the later confession and creeds. There was even a brief survey of “creedal elements” present in the New Testament. Formal creedal statements seem to have not emerged until the middle of the third century. However, “It is indisputable … that the root of all creeds is the formula of belief pronounced by the baptizand, or pronounced in his hearing and assented by him, before his baptism.”

The reader of the New Testament will continually come across creed-like sayings, which became slogans expressing the new faith. J.N.D. Kelly said in Early Christian Creeds that: “Creeds in the true meaning of the word were yet to come, but the movement towards formulation and fixity was under way.” Particular occasions, like when a candidate sought to be admitted to the Church, called for some kind of assurance of faith; some kind of statement of belief. So catechetical instruction and the baptismal rite itself called for declaring what you believed. Preaching was another occasion that would have lent itself to the formulation of doctrinal sayings.

The day-to-day polemic of the Church, whether against heretics within or pagan foes without, provided another situation [favorable] to the production of creeds. Yet another was supplied by the liturgy; solemn expressions of faith, in the form of hymns, prayers and devotional cries, had a natural place there.

“Jesus is Lord” or “Jesus is the Son of God” were simple, one-clause Christologies that appeared in Scripture as well as baptismal rites. There were also Binitarian (Jesus and God the Father) and Trinitarian (Father, Son and Holy Spirit) summaries of the Christian faith. Binitarian summaries like 2 Timothy 4:1—“I charge you in the presence of God and of Christ Jesus, who is to judge the living and the dead, and by his appearing and his kingdom”— were more common. But there were Trinitarian summaries as well, like 2 Corinthians 13:14 or the baptismal command of the Great Commission in Matthew 28:19-20: “Go therefore and make disciples of all nations, baptizing them in the name of the Father and of the Son and of the Holy Spirit, teaching them to observe all that I have commanded you.”

Paul gave what has all the appearance of being a summary of his gospel, drawn up for catechetical instruction or preaching in 1 Corinthian 15:3ff. “For I delivered to you as of first importance what I also received: that Christ died for our sins in accordance with the Scriptures, that he was buried, that he was raised on the third day in accordance with the Scriptures …” Or there is 2 Timothy 2:8, where he said: “Remember Jesus Christ, risen from the dead, the offspring of David, as preached in my gospel.” There are creed-like passages in: Romans 8:34, 1 Peter 3:18ff, Philippians 2:6-11, and others.

It was, after all, natural and inevitable that the initial proclamation of the gospel should emphasize the distinctively Christian, entirely novel and revolutionary element in the divine revelation. But the framework was there. It was always presupposed; and the firmness with which it was apprehended is evidenced by the extraordinary way in which the Binitarian and Trinitarian patterns wove themselves into the texture of early Christian thinking. In due course, with the development of catechetical teaching and of more systematic, comprehensive instruction in generally, as well as with the evolution of liturgical forms giving fuller expression to the faith, these vital aspects of it came to receive more regular and formal acknowledgement in creeds and semi-creedal summaries. . . . The impulse towards their formulation came from within, not from without; and at the New Testament stage we can observe the process in full swing, with confessions of all three types coexisting and interacting.

Above we noted how creeds emerged from a variety of sources, including preaching, liturgy, hymns prayers, devotionals and above all, baptismal initiation into the Church. In their traditional form, creeds are declaratory; they are short statements, in the first person, asserting belief in a selected group of facts and doctrines. Some declaratory professions of faith must have been part of the baptismal service of the early church. “In fact, it was precisely the need for a formal affirmation of belief to be rehearsed by the catechumen at baptism which instigated the Church to invent creeds in the first place.” Whatever their other uses may have been, “their primary raison d’être, was to serve as solemn affirmations of faith in the context of baptismal initiation.”

The Didache was most likely edited into its present form towards the end of the first century from materials written around 70 AD. The first known copy was not discovered until 1873, although there had been references to it by many ancient writers. It is composed of two parts: the “Two Ways” (1.1–6.2) and a manual of church order and practice (6.3–16.8). The Two Ways is a summary of basic instruction about the Christian life to be taught to those who were preparing for baptism and church membership. “In addition to providing the earliest evidence of a mode of baptism other than immersion, it records the oldest known Christian Eucharistic prayers and a form of the Lord’s Prayer quite similar to that found in the gospel of Matthew.”

The baptismal process of the early church was a series of questions asked of the individual, to which they would say: “I believe” before being submerged a series of three times, in a Trinitarian framework. The fourth century treatise by Ambrose, De Sacramentis, consists of six short addresses delivered to the newly baptized, which claimed it followed the Roman models as far as possible. The candidate entered the baptismal font and renounced the devil and his works, the world and its pleasures, and then:

You were questioned, “Dost thou believe in God the Father almighty?” You said, “I believe”, and were immersed, that is were buried. Again you were asked, “Dost thou believe in our Lord Jesus Christ and his cross?” You said: “I believe”, and were immersed. Thus you were buried along with Christ; for he who is buried along with Christ rises again with Him. A third time you were asked, “Dost thou believe also in the Holy Spirit?” You said, “I believe”, and a third time were immersed, so that your threefold confession wiped out the manifold failings of your earlier life.

During the first few centuries of the Church, the only “creeds,” loosely conceived, were ones directly connected with baptism. Yet their roots lay not so much in the rite of baptism, as in the catechetical training, which preceded it. Declaratory creeds were summaries of Christian doctrine “compiled for the benefit of converts undergoing instruction.” They can then be seen as a by-product of “the Church’s fully developed catechetical system.”

Additionally, by the 2nd century there was a “rule of faith” or a “canon of truth” believed and taught by the Church, and inherited from the Apostles. It just wasn’t an official, textually set confession of faith or creed. The content of that rule, in all it essentials, was foreshadowed by the “pattern of teaching” accepted in the apostolic Church. As was noted in “Legend of the Apostles’ Creed,” the early Church was a “believing, confessing, preaching Church,” with a collection of documents (the New Testament) telling “a unique story of redemption.”

As with the time of the New Testament itself, the writings of the Apostolic Fathers did not allude to any formal, official creed. But there was an abundance of “quasi-creedal scraps” which show that the creedal making impulses of the Christian communities were alive and active.” The author of 1 Clement (95/96 AD) echoed the Trinitarian pattern when he inquired of his readers, “Do we not have one God and one Christ and one Spirit of grace which was poured out upon us?” In the Shepherd of Hermas (95-100 BC?), is this comment on the first commandment: “First of all, believe that there is one God who created and finished all things, and made all things out of nothing. He alone is able to contain the whole, but Himself cannot be contained.” The letters of Ignatius have several quasi-creedal scraps, including this Binitarian pattern from To the Magnesians (110 AD): “There is one God who revealed himself through Jesus Christ his Son, who is his Word which came forth from silence.”

With Justin Martyr, we come across for the first time “what can plausibly be taken to be quotations of semi-formal creeds.” Justin converted to Christianity around 130. He was born in Nablus, in Palestinian Syria, and taught Christian philosophy after his conversion in Ephesus and later in Rome, where he opened a Christian school. In 165 he and some of his disciples were denounced as Christians and when they refused to sacrifice to pagan gods, they were scourged and beheaded.

The first thing to note is how deeply the Trinitarian pattern seems to have been reflected in his writings. Here in his first Apology (written In Rome around 150-155 AD), within a discussion on baptism, he said: “To the Father of the universe, through the name of the Son and of the Holy Ghost.” And again when discussing weekly worship: “We bless the Maker of all through His Son Jesus Christ, and through the Holy Ghost.” There is then another passage, again from his first Apology, that seems to be a loose paraphrase of a set, creed-like formula.

What sober-minded man, then, will not acknowledge that we are not atheists, worshipping as we do the Maker of this universe, and declaring, as we have been taught, that He has no need of streams of blood and libations and incense; whom we praise to the utmost of our power by the exercise of prayer and thanksgiving for all things wherewith we are supplied, as we have been taught that the only honour that is worthy of Him is not to consume by fire what He has brought into being for our sustenance, but to use it for ourselves and those who need, and with gratitude to Him to offer thanks by invocations and hymns for our creation, and for all the means of health, and for the various qualities of the different kinds of things, and for the changes of the seasons; and to present before Him petitions for our existing again in incorruption through faith in Him. Our teacher of these things is Jesus Christ, who also was born for this purpose, and was crucified under Pontius Pilate, procurator of Judæa, in the times of Tiberius Cæsar; and that we reasonably worship Him, having learned that He is the Son of the true God Himself, and holding Him in the second place, and the prophetic Spirit in the third, we will prove.

Kelly said it was difficult to resist the conclusion that Justin knew of “a developed Christological kerygma [an irreducible essence of Christian apostolic preaching], which already enjoyed a measure of fixity.” However, there is no evidence it was “an official declaratory creed used at Rome or in any other church.” Nevertheless, as early as the time of Justin “there was apparently something approaching a settled form for the baptismal questions.” Irenaeus and Tertullian knew of formularies, which seemed to have an official character and a distinctive outline, even if their wording wasn’t always given verbatim.

By the middle of the third century the process of crystallization had gone a very long way: there were (and had been, we may conjecture, for some time) “customary and established words”. The endorsement of the local ecclesiastical authority, it would seem, had been added. The framework of the questions was always and everywhere the Lord’s baptismal command, the candidate being asked three times whether he believed in the Father, the Son and the Holy Spirit. Gradually these bare interrogations were expanded.

For more on the early creeds and heresies of the Christian church, see the link: “Early Creeds.”

02/16/18

Conjuring Diagnoses for the Elderly

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In 2005, the FDA required atypical antipsychotics to carry a boxed warning that they had a higher risk of death related to use among individuals with dementia. In 2008, the FDA required the same warning with the older, typical antipsychotics. Antipsychotic use in nursing homes is now closely watched by government regulators, “who penalize and lower the ratings of facilities that overuse them.” This created an opportunity for the manufacturer of a little-used medication known as Nuedexta. Since 2012, there has been an increase of nearly 400% in the number of Nuedexta pills dispensed to long-term care facilities.

A CNN investigation reported on how “The maker of a little red pill intended to treat a rare condition is raking in hundreds of millions of dollars a year as it aggressively targets frail and elderly nursing home residents.” Nuedexta is approved to treat a disorder known as pseudobulbar affect or PBA. The disorder is a condition that causes sudden, uncontrollable crying and/or laughing. PBA afflicts less than 1% of all Americans and is most commonly found in people with multiple sclerosis (MS) or Lou Gehrig’s disease (ALS). The manufacturer of Nuedexta, Avanir, had its sales force focus on expanding the drug’s use with elderly patients struggling with dementia and Alzheimer’s disease. See the following graphic from CNN on the number of Nuedexta pills dispensed to long-term facilities.

Nuedexta is approved by the Food and Drug Administration (FDA) to treat anyone with PBA, including those with a variety of neurological conditions such as dementia. But geriatric physicians, dementia researchers and other medical experts told CNN that PBA is extremely rare in dementia patients; several said it affects 5% or less. And state regulators have found doctors inappropriately diagnosing nursing home residents with PBA to justify using Nuedexta to treat patients whose confusion, agitation and unruly behavior make them difficult to manage.

CNN identified dozens of examples across the country where the use of Nuedexta was questionable. In one Los Angeles nursing home, regulators found that 28% of its 162 residents had been placed on Nuedexta. A facility psychiatrist, who is a paid speaker for Avanir, had given a talk about the drug to nursing home employees. An employee at another Southern California facility admitted a resident was given a diagnosis of PBA in order to justify the use of Nuedexta, “even though its intended purpose was to control the resident’s “mood disturbances” and yelling out.” An Ohio doctor has come under investigation for allegedly receiving kickbacks for fraudulently diagnosing PBA in order to get Medicare coverage for Nuedexta.

The federal government foots the bill for a big portion of the money being spent on Nuedexta in the form of Medicare Part D prescription drug funding, for people 65 and over and the disabled. In 2015, the most recent year for which data is available, this Medicare program spent $138 million on Nuedexta — up more than 400% from just three years earlier.

The only FDA approved medication for patients with PBA is Nuedexta. “So experts say that Medicare coverage of the drug, which has been crucial to its financial success, relies on the diagnosis of this single condition.” Off-label prescribing of Nuedexta to treat patients with behavioral issues who were not diagnosed with PBA would likely not be covered. CNN analysis found that almost half of the Nuedexta claims filed with Medicare in 2015 “came from doctors who had received money or other perks from the company [Avanir].”

During the FDA approval process, two doctors on the committee raise concerns about Nuedexta being used for PBA in Alzheimer’s patients. “They both strongly recommended that Nuedexta only be approved for PBA in patients with MS or ALS.” Evidence, they argued, that it would be effective in other conditions was weak; and not enough was known about the safety of the drug in the elderly. Despite these concerns, the FDA did not limit its use as recommended. “The agency approved Nuedexta in 2010 for treating PBA in patients who have neurological conditions such as dementia.”

Soon after it hit the market, Neudexta was getting reports of potential harm, ranging from dizziness and falls to coma and death. “Nuedexta was listed as a ‘suspect’ medication in nearly 1,000 so-called adverse event reports received by the FDA detailing side effects, drug interactions and other issues.” It was listed by caregivers as a potential cause of 133 hospitalizations (which included 8 cases that also resulted in death), 51 deaths, 102 incidents of sedation and sleepiness and 101 of dizziness, confusion and falls. A nurse practioner reported on an 86-year-old Alzheimer’s patient who rapidly declined after Nuedexta was added to her Zoloft (an antidepressant), Xanax (an antianxiety medication) and Risperidone (an antipsychotic). Almost immediately she declined and became almost unresponsive, ultimately dying.

Nuedexta is a combination of two generic drugs, dextromethorphan and quinidine that are respectively a cough suppressant and antiarrhythmic drug (it slows rapid heartbeat and helps your heart beat regularly). They were once available from specialty pharmacists for less than $1 a pill. The FDA-approved medication now costs as much as $12.60 a pill; more than $9,000 a year. “Medicare Part D spending on the drug averaged $3,400 per patient in 2015.” It gained public attention through a television commercial featuring actor Danny Glover cycling through fits of laughing and crying.

Avanir executives have wanted to secure FDA approval for Nuedexta’s use to treat dementia patients who don’t have PBA, “setting their sights on the more widespread condition of agitation in dementia and Alzheimer’s patients, characterized by emotional and physical outbursts and restless behaviors.” A study has been completed that looked at the efficacy, safety and tolerability of Neudexta for the treatment of agitation in Alzheimer’s patients, but the results haven’t been posted. “Without additional FDA approval for the drug’s use in those conditions, salespeople cannot promote Nuedexta for that purpose. They can only market its use for dementia patients who also have PBA.”

Across the country, the use of Nuedexta in nursing homes has prompted concerns among state regulators whose job is to ensure adherence to federal guidelines and protect residents from being given unnecessary drugs — especially those used as chemical restraints. But to date, the red flags raised by these regulators have been largely left buried in nursing home inspection reports and have drawn little public attention.CNN identified more than 80 cases in 19 states since 2013 where inspectors cited nursing homes for inappropriate monitoring and use of Nuedexta — often because residents hadn’t exhibited any symptoms of PBA. Many of the cases — about 40% — were clustered in Southern California, where Avanir is based and where former employees said there has been aggressive marketing.

Currently there are no FDA-approved drugs to treat dementia-related agitation. But those who care for the elderly are eager to find tools to manage agitated and aggressive patients. Staff increases could reduce the need for medications. But these measures don’t always work and they are expensive. So some facilities use pharmaceuticals to help make their patients easier to treat. Helen Kales, a geriatric psychiatrist said: “”Rather than taking someone off an antipsychotic … providers search for a different ‘magic bullet.'”

McKnight’s Long-Term Care News reported that The Centers for Medicare & Medicaid Services said that it met its goal of reducing the national rate of antipsychotic use among long-term residents by 20% by the end of 2016. However, Winter et al. reported in Clinical Gerontologist there was a 12% increase for the combined rates of schizophrenia, Tourette’s and Huntingdon’s among long-term residents. The increase began in 2012 at a rate almost triple that of the general long-term nursing home population. Most of the increase was in the rates of schizophrenia reported. The increased “identification” of these psychiatric conditions seems new “and concentrated in residents on antipsychotics.”

Since antipsychotics prescribed for schizophrenia, Tourette’s, and Huntington’s are excluded from quality-measure auditing, apparent reductions in inappropriate long-stay antipsychotic use since the National Partnership may be exaggerated.

Sadly it seems that despite the clear evidence of adverse effects from antipsychotics and Nuedexta with the elderly, long-term care facilities have simply conjured up a diagnosis to justify their use.

02/13/18

Keep Marijuana Medical in PA

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Western Pennsylvania is about to see medical marijuana sales begin. Two dispensaries are scheduled to open on February 15th, 2018. It’s been almost two full years since Governor Tom Wolf signed Senate Bill 3, legalizing medical marijuana on April 17, 2016. As the Governor signed the bill, he said: “I am proud to sign this bill that will provide long overdue medical relief to patients and families who could benefit from this treatment.” At the time, the press release expected implementing the state’s Medical Marijuana Program to take between 18 and 24 months, making it right on schedule. Let’s hope that what’s coming sets PA on a different path than California’s original legalization of medical marijuana did in 1996—despite the hopes of two of the sponsors of the new PA law.

When Proposition 215 was about to be approved in California, Senator Diane Feinstein said: “you’ll be able to drive a truckload of marijuana through the holes in it.” The devil is in the details, and she said that particular bill lacked details. A significant difference between Proposition 215 and the Pennsylvania Medical Marijuana Program is that in PA, dried leaves, plant material and edibles are strictly prohibited. Grower/processors can only manufacture the forms of medical marijuana listed in Act 16. These include: 1) a form medically appropriate to administer by vaporization or nebulization; 2) pills; 3) topical forms, including gels, creams or ointments; 4) tinctures; 5) liquids; or 6) oils. A licensed practitioner or medical professional determines which form is appropriate for the patient.

Cannabis products as they are to be sold in PA will provide medical relief to patients and families within the state without the patent medicine aura in dispensaries hocking different kinds of edibles or plant material for what “ails” you, as in states with less restrictive medical marijuana laws (like California). A medical professional (physician, physician assistant or certified registered nurse) has to be present during all hours a facility is open and offering to dispense or consult with a patient. Additionally, they all have to complete a required four-hour training and be registered with the PA Department of Health. Significantly, “a practitioner or physician may not issue a patient certification at the dispensary facility.”

Patients wanting to participate in the medical marijuana program have to visit the online Patients and Caregivers Registry and create a profile in the Department of Health’s patient and caregiver registry. Then they have to obtain a physician’s certification they suffer from one of the 17 serious medical conditions listed in the graphic below. Returning to the Patients and Caregivers Registry, they pay $50 a year for a medical marijuana ID card. Caregivers for minors or patients unable to travel to a dispensary themselves can also participate in the medical marijuana program. Registered caregivers can have up to five patients. See the YouTube video, “Overview of Medical Marijuana in Pennsylvania” on the webpage for more information on the Pennsylvania Medical Marijuana Program linked above.

Look on the website for other resources such as a list of approved practitioners by state region and county, the Patient and Caregiver Registry, and an Information for Patients Brochure. Under certain guidelines, a parent, legal guardian or caregiver may administer medical marijuana to students with serious medical conditions while on school property. See the website for more information on what is required for this process.

The initial guidelines described above will give patients in Pennsylvania access to marijuana for legitimate medical reasons. If the guidelines are followed as described above, they will help the state avoid its new medical marijuana program morphing into what has happened in California since the approval of Proposition 215 in 1996. But Pennsylvania citizens and government officials need to be vigilant. At least two of the cosponsors of the legislation itself want to see the plant form of marijuana available for sale in dispensaries and to eventually to see the state move towards legalizing recreational marijuana.

In April of 2017 at the World Medical Cannabis Conference & Expo held in Pittsburgh, one of the sponsors of Senate Bill 3 (SB 3), State Senator Daylin Leach, said he expected medical marijuana would be available in plant form in dispensaries sometime during 2018. He noted a section of the bill authorizes an advisory board to make recommendations by April of 2018 about whether to change the permissible forms of the drug. During a panel discussion at the Expo, Margaret Sun for WESA reported Leach said the following about the advisory board:

“But they will [approve sale of the plant form of marijuana], because we’re appointing people to do that,” Leach said as the crowd laughed. “They will recommend that at latest by April 17 (2018), which means when dispensaries open, it is likely that they will have whole plant on their shelves from day one.”

Leach’s statement went over well with his listeners, but his ability to make good on his promise is more bluster than reality. What follows is a description of the members of the Medical Marijuana Advisory Board within the State Department of Health are supposed to include. I don’t see him being able to stack this deck:

Members include the Secretary of Health; the Physician General; State Police Commissioner; Chair of the State Board of Pharmacy; Commissioner of Professional & Occupational Affairs; President of the Pennsylvania Chiefs of Police Association; President of the Pennsylvania District Attorneys Association; members to be appointed by the Governor and the four legislative caucuses who are knowledgeable and experienced in issues relating to care and treatment of individuals with a serious medical condition, geriatric or pediatric or clinical research. One member appointed by the Governor shall be a patient, a family or household member of a patient or a patient advocate.

Also, the Department of Health has the final approval on whether to add the smokeable plant form to the program, but as SB 3 is written—and as it is now described on the website—dried leaves, plant material and edibles are not approved. Leach’s words suggest his intentions in sponsoring the medical marijuana legislation was at least partly as a stepping stone to his intent to pursue full legalization of recreational marijuana. Both Leach and another sponsor of SB 3, State Senator Mike Folmer, said they thought full legalization was inevitable in Pennsylvania. Folmer stated he couldn’t politically advocate for legalization just now, as it was difficult enough getting Republicans on board with the medical marijuana program. He said:

I’d like to see our first dispensaries up, I’d like to see the first grower/processors going, and I think then, on my side, we’ll see that the sky isn’t going to fall, dogs won’t sleep with cats, and the sun will still set in the West and civilization will not crumble.

Civilization won’t crumble with the implementation of the existing PA Medical Marijuana Program. But our inability to trust disingenuous politicians who pragmatically use public sympathy for suffering individuals to further their political agendas will crumble our civilization. SB 3 was apparently a backdoor strategy for these two PA State Senators towards their desire to eventually legalize recreational marijuana. Was there ever any real concern for the needs of medical marijuana patients, or was it just rhetoric to get closer to recreational legalization? Leach is a Democrat from Montgomery County and Folmer is a Republican representing Dauphin, Lebanon and York Counties. Remember this if you live in the areas they represent as their term expires.

The Pennsylvania Medical Marijuana Program as it now exists will provide for suffering individuals within the state. And that is a good thing. Other than THC (the psychoactive cannabinoid in cannabis), there seems to be a significant medicinal potential with CBD (cannabidiol). Further research is needed and the federal classification as a Schedule I substance hampers that research from being done. That needs to change.

There are some serious researchers, like Staci Gruber, who are investigating the medical benefits of cannabis without being blinded to its potential adverse psychoactive harms. PA medical marijuana research would do well to partner with researchers like Gruber and her organization, MIND (Marijuana Investigations for Neuroscientific Discovery). Let’s let research and not rhetoric guide the medical uses of the cannabinoids in cannabis. So far it seems there are limited health benefits from THC. See “Listening to Marijuana Research” for more information on this.

Solevo Wellness is set to open its doors for business in the Squirrel Hill section of Pittsburgh on February 15th. The dispensary’s first shipment is coming from the grower-processor Cresco Yeltrah in Brookville, Jefferson County. Visitors will be greeted by a receptionist and show their necessary legal paperwork to gain access to products and then visit with a pharmacist. “Then they’ll head to a showroom, where cannabis product samples are kept inside glass cases, make a purchase and continue with their day.” The Solevo Wellness dispensary is constantly monitored by security cameras.

CY+ opened its doors with a ribbon cutting ceremony in Butler PA on February 1st. It will begin selling its products on the fifteenth as well. Larry Clark, the Pennsylvania Deputy Director of Medical Marijuana was there. He said: “It’s a medical experience”; not the head shop approach. Kimberly Geyer, the Butler County Commissioner, said: “It defies all the traditional stereotypes associated with this industry.” CY+ is owned by Cresco Yeltrah, which seems to be a subsidiary of Cresco Labs, a company out of Chicago. Charlie Bachtell, the cofounder of CY+, was at the opening in Butler. Bachtell is the CEO and Cofounder of Cresco Labs. They hope to open their second Western Pennsylvania facility in the Strip district by mid-April.

That’s just around the time Daylin Leach thought the state advisory board could approve the sale of plant product in stores. Given the difficulty it seems there was in getting SB 3 passed not only does that seem unlikely, but it would be political suicide for medical marijuana activists. Dispensing marijuana as a medical product in an environment that has the feel of a medical practice or medicine shop rather than a head shop sets the right tone. Trying to force the so-called progressive cause of legalizing recreational marijuana on the back of the recent approval of medical marijuana could sink them both in PA. But Leach may have other things on his mind since his brash claim last year at the World Medical Cannabis Conference & Expo.

Daylin Leach had an event-filled 2017. He temporarily moonlighted as a lawyer for a Philadelphia law firm that lobbies for the marijuana industry from shortly after Governor Wolf signed SB 3 until he announced a run for Pennsylvania’s 7th Congressional District in July of 2017. He then announced the suspension of his campaign in December of 2017 in the midst of accusations of a pattern of inappropriate behavior with several former female staffers. He took this step after a story in the Philadelphia Inquirer appeared in which a series of former campaign and legislative staffers accused him of inappropriate behavior. He said he was taking a step back to focus on his family and work with Senate leaders to address these allegations. “I will continue to do all that I can to advance progressive causes in the Senate and represent my constituents with honor.”

Frankly, I think he’s done enough and needs to move on to another progressive cause besides legalizing marijuana. But I suspect the financial lure of cannabis might be too strong for him to resist. So let’s make other PA state legislators aware of wanting to keep marijuana medical in PA.

02/9/18

Legend of the Apostles’ Creed

© jorisvo | 123rf.com – fresco (1450) depicting the articles of the Apostles’ Creed.

The Apostles’ Creed has been a central part of worship and declaring what individuals and congregations believe about the members of the Trinity since the early centuries of the Christian church. For centuries it was believed that after Pentecost and before the apostles dispersed in the Great Commission, they “mutually agreed upon a standard of their future preaching.” They were said to have developed this standard so that when they were separated, they would not unintentionally vary “in the statements which they should make to those whom they should invite to believe in Christ.” Yet it seems this origins tale for the Apostles’ Creed is just a legend.

The fourth century monk and historian, Rufinus Tryannius wrote a commentary on the Apostles’ Creed, probably around 307-309 AD. In his commentary Rufinus related the above origins story for the Creed which was widely believed in the Western Christian church until the 15th century. Each of the apostles, “filled with the Holy Ghost,” were said to have contributed several sentences to the one common summary, which later became known as the Apostles’ Creed. Rufinus said:

Our forefathers have handed down to us the tradition, that, after the Lord’s ascension, when, through the coming of the Holy Ghost, tongues of flame had settled upon each of the Apostles, that they might speak diverse languages, so that no race however foreign, no tongue however barbarous, might be inaccessible to them and beyond their reach, they were commanded by the Lord to go severally to the several nations to preach the word of God. Being on the eve therefore of departing from one another, they first mutually agreed upon a standard of their future preaching, lest haply, when separated, they might in any instance vary in the statements which they should make to those whom they should invite to believe in Christ. Being all therefore met together, and being filled with the Holy Ghost, they composed, as we have said, this brief formulary of their future preaching, each contributing his several sentence to one common summary: and they ordained that the rule thus framed should be given to those who believe.

The Apostles’ Creed itself was present and increasingly became an important summary of confession and belief in the life of the church from at least the time of Rufinus in the late 3rd and early 4th centuries. In his 5th century treatise on Christian piety, the Enchiridion, Augustine explained how the Apostles’ Creed was useful in teaching Christian doctrine and in refuting heresies. Along with the Lord’s Prayer, he thought the Creed was a succinct summary of the Christian doctrine and faith.

For you have the Creed and the Lord’s Prayer. What can be briefer to hear or to read? What easier to commit to memory?When, as the result of sin, the human race was groaning under a heavy load of misery, and was in urgent need of the divine compassion, one of the prophets, anticipating the time of God’s grace, declared: “And it shall come to pass, that whosoever shall call on the name of the Lord shall be delivered [Joel 2:32].” Hence the Lord’s Prayer. But the apostle, when, for the purpose of commending this very grace, he had quoted this prophetic testimony, immediately added: “How then shall they call on Him in whom they have not believed [Romans 10:14]?” Hence the Creed. In these two you have those three graces exemplified: faith believes, hope and love pray.

The above legend was an accepted part of the history of the church until the Council of Florence (1438-1445), which attempted a reunification of the Western and Eastern churches. At the beginning of the negotiations, the Western, Latin representatives invoked the Apostles’ Creed. In response, the Eastern Greek representatives said they did not possess and had never seen “this creed of the Apostles.” Moreover, as J.N.D. Kelly quoted Marcus Eugenicus in Early Christian Creeds, “If it had ever existed, the Book of Acts would have spoken of it in its description of the first apostolic synod at Jerusalem, to which you appeal.”

Once the question is squarely faced, the extreme unlikelihood of the Apostles having drafted an official summary of faith scarcely merits discussion. Since the Reformation the theory that they did has been quietly set aside as legendary by practically all scholars, the conservative-minded merely reserving the right to point out that the teaching of the formula known as the Apostles’ Creed reproduces authentically apostolic doctrine.

Kelly went on to say the legend is an example of the tendency of the early Church to “attribute the whole of its doctrinal, liturgical and hierarchical apparatus” to the Twelve Apostles, and through them to Christ himself. He said this could be acknowledged without prejudice to the question of whether 2nd century Church fathers were correct to claim their rule of faith was the same as the faith of the Apostles. If the question was “Did the apostolic Church possess an official, textually determined confession of faith” the answer is no, it did not. However, “creeds of a looser sort,” that lacked the fixed and official character of the later formularies—yet clearly foreshadowing them—were is use early on.

The early Church was a “believing, confessing, preaching Church.” If the Christians of the apostolic age had not seen themselves as possessing a body of distinctive, consciously held beliefs, why would they have separated from Judaism and begun their program of missionary expansion? “Everything goes to show that the infant communities looked upon themselves as the bearers of a unique story of redemption.” The New Testament is a collection of documents written “from faith to faith.”

The Gospels carefully elaborate certain dogmatic beliefs about Jesus, “which they seek to explain and justify.” The other documents “presuppose a background of faith shared by the author and those for whom he is writing.” For all their differences of nuance, the documents of the New Testament “comprise a body of literature which could only have sprung from a community with a strongly marked outlook of its own.”

In light of these considerations it is impossible to overlook the emphasis on the transmission of authoritative doctrine which is to be found everywhere in the New Testament. In the later strata the reference to an inherited corpus of teaching are clear enough. In Jude 3, for example, we read of “the faith once delivered to the saints”; later (verse 20) the author speaks of “your most holy faith”, again using the word in the sense of an accepted body of beliefs.

Further examples given by Kelly were from the Pastoral Epistles, including 1 Timothy 6:20; 2 Timothy 1:13; Titus 1:9. Hebrews advises its readers to “hold fast our confession;” without wavering (Hebrews 4:14, 10:23). In 2 Thessalonians 2:15 Paul exhorted his readers to “stand firm and hold to the traditions that you were taught by us, either our spoken word or our letter.” In Romans 6:17 Paul referred to the “standard of teaching to which you were committed.”

What we have before us, at any rate in rough outline, is the doctrinal deposit, at the pattern of sound words, which was expounded in the apostolic church since its inauguration and which constituted its distinctive message.

The story that the Twelve met and composed an “Apostles’ Creed” is a pious fiction. But by the 2nd century there was a “rule of faith” or a “canon of truth” believed and taught by the Church, and inherited from the Apostles. It just wasn’t an official, textually set confession of faith or a creed, as with the Apostles’ Creed and others that followed. The content of that rule, in all it essentials, was foreshadowed by the “pattern of teaching” accepted in the apostolic Church. Its essentials were prototypically contained in the New Testament. From the end of the first century to the middle of the third century, there were only creeds in this elastic, nontechnical sense of the term. “That the Church in the apostolic age possessed a creed in the broad sense of a recognized body of teaching may be accepted as demonstrated fact.”

For more on the early creeds and heresies of the Christian church, see the link: “Early Creeds.”

02/6/18

Preying on Academics

© kamchatka | stockfresh.com

Seeking to test whether “predatory” journals would publish an obviously absurd paper, the science blogger Neuroskeptic wrote a Star Wars-themed spoof. His paper was about “midi-chlorians,” which in the Star Wars universe are entities that live inside cells and give the Jedi their powers. He filled the paper with other references to the “galaxy far, far away,” and submitted it to nine journals under the names of Dr. Lucas McGeorge and Dr. Annette Kim. Three journals accepted and published the spoofed article; another offered to publish it for a fee of $360.

Within six days of Neuroskeptic publishing his blog article describing what he did, “Predatory Journals Hit By ‘Star Wars’ Sting,” all three journals had deleted his online journal article. To generate the main text of the paper, he copied the Wikipedia page on “mitochondrion,” which actually do exist, and replaced all references in it with the Star Wars term “midichlorians.” He even admitted how he had reworded the text in the Methods section of his spoofed paper, saying: The majority of the text in the current paper was Rogeted from Wikipedia.” Oh, and “Dr. Lucas McGeorge” was sent an unsolicited invitation to serve on the editorial board of one of the journals. Some of clues within his article indicating it was a spoof included the following:

“Beyond supplying cellular energy, midichloria perform functions such as Force sensitivity…”“Involved in ATP production is the citric acid cycle, also referred to as the Kyloren cycle after its discoverer”“Midi-chlorians are microscopic life-forms that reside in all living cells – without the midi-chlorians, life couldn’t exist, and we’d have no knowledge of the force. Midichlorial disorders often erupt as brain diseases, such as autism.”

Neuroskeptic said his sting doesn’t prove that scientific publishing is hopelessly broken, but it does provide a reminder that at some so-called peer reviewed journals, there is not any “meaningful peer review.” This was an already known problem, but his sting illustrates the importance of peer review, which “is supposed to justify the price of publishing.” If you’re interested in reading the spoofed paper, there is a link in his blog article.

This matters because scientific publishers are companies selling a product, and the product is peer review. True, they also publish papers (electronically in the case of these journals), but if you just wanted to publish something electronically, you could do that yourself for free.

Neuroskeptic referred to another article found in the New York Times that was also about a “sting” operation on predatory journals. Here, a fictitious author, Anna O. Szust (Oszust is the Polish word for ‘a fraud’), applied to 360 randomly selected open-access journals asking to be an editor. Forty-eight accepted her and four made he editor in chief. She received two offers to start new journals and be the editor. The publications in her CV were fake, as were her degrees. “The book chapters she listed among her publications could not be found, but perhaps that should not have been a surprise because the book publishers were fake, too.”

Dr. Fraud received some tempting offers. She was invited to organize a conference, whose papers would be published. She would get 40% of the proceeds. Another journal invited her to start a new journal and offered her 30% of the profits. The investigators who conceived this sting operation told the journals that accepted Dr. Fraud that she wanted to withdraw her application to be an editor. “Dr. Fraud remains listed as a member of the editorial boards of at least 11 of those journals.”

Dr. Pisanski and her colleagues wrote about their sting operation in the journal Nature: “Predatory Journals Recruit Fake Editor.” Pisanski et al. said they became increasingly disturbed at the number of invitations they received to become editors or to review journals that were outside of their field. They learned some colleagues, mainly early-career researchers, were unaware of these predatory practices and had fallen for these traps.

So, in 2015, we created a profile of a fictitious scientist named Anna O. Szust and applied on her behalf to the editorial boards of 360 journals. Oszust is the Polish word for ‘a fraud’. We gave her fake scientific degrees and credited her with spoof book chapters. Her academic interests included, among others, the theory of science and sport, cognitive sciences and methodological bases of social sciences. We also created accounts for Szust on Academia.edu, Google+ and Twitter, and made a faculty webpage at the Institute of Philosophy at the Adam Mickiewicz University in Poznań. The page could be accessed only through a link we provided on her CV.

The aim of their study was to help academics understand how bogus versus legitimate journals operate—not trick the journals into accepting them as an editor. So if journals did not respond to her application, they did not email them again. “In many cases, we received a positive response within days of application, and often within hours.” They coded journals as “Accepted” only when a reply to their email explicitly accepted Szust as an editor or if Szust’s name appeared as an editorial board member on the journal’s website.

The laudable goal of open-access publishing gave birth to these predatory journals. Traditional academic journals raise support by subscription fees, while authors pay nothing. “Open-access journals reverse that model. The authors pay and the published papers are free to anyone who cares to read them.” For example, the Public Library of Science (PLOS) journals (which are credible open-access journals), charges between $1,495 and $2,900 to publish a paper. Predatory journals exist by publishing just about anything sent to them for a fee, often between $100 and $400, according to Jeffrey Beall, a scholarly communications librarian at the University of Colorado.

Beall does not believe that everyone who publishes in these predatory journals is duped. He thinks many researchers know exactly what they are doing when they publish an article there. “I believe there are countless researchers and academics, currently employed, who have secured jobs, promotions, and tenure using publications in pay-to-publish journals as part of their credentials and experience for the jobs and promotions they got.” So it now requires some due diligence on the part of academic employers to ferret out those questionable publications.

In “Science is Broken,” Siddhartha Roy and Marc Edwards, noted how over the past fifty years, “the incentives and reward structure of science have changed, creating a hypercompetition among academic researchers.” Universities are now using part time and adjunct faculty for up to 76% of their academic labor force. This makes tenure-track positions rarer and more desirable, as universities operate more like businesses. This academic business model has also led to an increased reliance on quantitative performance metrics “that value numbers of papers, citations and research dollars raised has decreased the emphasis on socially relevant outcomes and quality.”

There is growing concern that these pressures may encourage unethical conduct by some scientists. It certainly has contributed to the replication problem with published studies. See “Reproducibility in Science” for more on the replication problem. Roy and Edwards said: “We believe that reform is needed to bring balance back to the academy and to the social contract between science and society, to ensure the future role of science as a public good.” Predatory journals have entered into this changing structure of the academic business model, seeing the opportunity to take advantage of the “publish or perish” pressure on academics to secure jobs, promotions and gain tenure. The result has been an undermining of the university system and the practice of science as a public good.

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.