04/23/24

Corruption Caused by Indwelling Sin

Image by Klaus Hausmann from Pixabay

In chapter fifteen of Indwelling Sin, John Owen said he would now consider the many ways indwelling sin habitually corrodes grace and holiness in believers. At first, believers have many fresh springs and refreshing showers coming upon them, filling them up with a high rate of faith, love holiness, fruitfulness, and obedience. As it is with a flood, when these many streams run into a river, the river swells over its bounds, “and rolls on with more than ordinary fullness.” But if these springs are not kept open, if they don’t continue with an abundance of these showers, “they must needs decay and go backwards.”

One of these springs is a fresh, vigorous sense of pardoning mercy. Accordingly, when this is in a person’s soul, it results in the love and delight of God and leads to obedience to His will. “As, I say, is the sense of gospel-pardon, so will be the life of gospel-love.” Consider the sinful woman described in Luke 7:36 and following.

When a Pharisee had asked Jesus to eat with him, a woman who was known to be a sinner came and kissed his feet and anointed them with ointment. The Pharisee thought to himself, if Jesus were a true prophet, he would know what sort of woman is touching him, for she is a sinner. Knowing his thoughts, Jesus told him a parable about a moneylender and two debtors and asked which debtor loved him more. The Pharisee judged it was the one for whom the money lender cancelled the larger debt. Jesus confirmed he had judged rightly and then said to Simon:

Do you see this woman? I entered your house; you gave me no water for my feet, but she has wet my feet with her tears and wiped them with her hair. You gave me no kiss, but from the time I came in she has not ceased to kiss my feet. You did not anoint my head with oil, but she has anointed my feet with ointment. Therefore I tell you, her sins, which are many, are forgiven—for she loved much. But he who is forgiven little, loves little. (Luke 7:44-47)

So, when sinners are first converted, they are very sensible to their great forgiveness. Their recognition of the greatness of their sin greatly subdues their hearts and spirits to God, “and quickens them to all obedience.” Even cursed sinners as they were could be delivered and pardoned. “The love of God and of Christ, in their forgiveness, highly conquers and constrains them to make it their business to live to God.”

A second spring is the fresh taste they have of spiritual things that has such a savor and relish in their souls, that worldly pleasures are rendered sapless and undesirable. After tasting the wine of the gospel, they desire no other. When souls are first translated into the light of Christ, they see a new glory that defiled the desirableness of all earthly diversions. “They see a new guilt and filth in sin, that gives them an utter abhorrency of its old delights and pleasures.”

It’s as if a man that was kept a long time in a dungeon was brought forth suddenly into the sun light. He’d find so much pleasure and contentment in the beauties of the creation that he’d think he could never weary of it. Nor would he ever be content to be under darkness—for any reason—ever again. So it is with people when they are first translated into the marvelous light of Christ to behold the beauty of the new creation. “They see a new glory in him, that hath quite sullied the desirableness of all earthly diversions. And they see a new guilt and filth in sin, that gives them an utter abhorrency of its old delights and pleasures.”

The first way, then, that indwelling sin prepares individuals for decays and corruption in grace and obedience is it strives to stop or taint these springs by sloth or negligence. It prevails on the soul to forget or neglect thinking about the things that so powerfully influenced it to strict and fruitful obedience. If care is not taken, if the person is not diligent and watchful of the means appointed by God to maintain a living sense of them upon them, “they will dry up and decay.” And the obedience that should spring from them will as well.

Let the heart ever so little disuse itself to gracious, soul-affecting thoughts of the love of God, the cross of Christ, the greatness and excellency of gospel-mercy, the beauties of holiness; they will quickly be as much estranged to a man, as he can be to them.

Another way that indwelling sin works to taint these springs is to encourage formal, weary, powerless thoughts of those things which it should overcome in diligence thankful obedience. God said through Moses to Aaron he will be sanctified in all those who are near him (Leviticus 10:3). So are we to deal with the things of God whereby we have communion with him. When we begin to entertain them with slight and common thoughts, not using and improving them to the utmost, they lose all their beauty, and glory, and power towards them.

When we have anything to do, wherein faith, or love towards God is to be exercised, we must do it with all our hearts, with all our minds, strength, and souls, not slightly and carelessly, which God abhors; he does not only require that we bear his love and grace in remembrance, but that, as much as in us lies, we do it according to the worth and excellency of them.

So, when we consider gospel truths, we should strive to be changed into the same image or likeness (2 Corinthians 3:18). Otherwise, it will be like James tells us: “He is like a man who looks intently at his natural face in a mirror. For he looks at himself and goes away and at once forgets what he was like” (James 1:23-24). It makes no impression upon him because he does it only slightly. They talk of religion and spiritual things as much as they ever did in their lives, and perform duties with as much steadfastness as they ever did.

But yet have poor, lean, starving souls, as to any real and effectual communion with God. By the power and subtlety of indwelling sin, they have grown formal, and learned to deal about spiritual things in a careless manner, whereby they have lost all their life, vigour, savour, and efficacy towards them. Be always serious in spiritual things, if ever you intend to be bettered by them.

Indwelling sin will often stop these springs of gospel obedience by false and foolish opinions, corrupting the simplicity of the gospel. “False opinions are the works of the flesh.” They mostly come from the vanity and darkness of the minds of men with a mixture of corrupt affections. Owen said they have seen some who after they had received “a sweet taste of the love of God in Christ,” and walked with him for many years, despised all their own experiences and rejected the efficacy of truth. “We have innumerable instances hereof in the days wherin we live.”

Owen goes on in the chapter to describe how Satan is a diligent, watchful, and crafty adversary. “He will neglect no opportunity, no advantage that is offered to him.” Wherever our spiritual strength is impaired by sin, or however our lusts pressure, Satan falls in with that weakness, and presses towards that ruin.” He gives his readers a few cautions to keep them from this corruption.

First, there are a great number of hypocrites in the body of believers. For others, you don’t know what the present temptations they struggle against. There may be some secret lust in their heart that the soul contends against faintly. But it does not make thorough work, vigorously mortifying it by the strength and power of grace.

But where indwelling sin has provoked, irritated, and given strength to a special lust, it proves assuredly a principal means of a general declension. For as an infirmity and weakness in any one vital part, will make the whole body consumptive, so will the weakness in anyone grace, which a perplexing lust brings with it, make the soul. It every way weakens spiritual strength.

Yet there is hope. Owen said a great sin will certainly give a great turn to the life of a believer. If it is cured in the blood of Christ, with the humiliation that the gospel requires, “it often proves a means of more watchfulness, fruitfulness, humility, and contention, than ever the soul before obtained.” If neglected, it certainly hardens the heart and weakens spiritual strength, enfeebles the soul, and discourages all communion with God. But if like a broken bone which is well set, it leaves the person stronger than before. If otherwise, it makes the person a cripple all their days.

These are the corruptions caused by indwelling sin.

04/16/24

Psychedelics as the Newest Psychiatric Craze, Part 2

Image by Gordon Johnson from Pixabay

On December 12, 2023 the MAPS Public Benefit Corporation announced it submitted a new drug application (NDA) to the FDA for MDMA-assisted therapy. MAPS PBC (now called Lykos Therapeutics) requested the FDA grant a priority review, given that MDMA received a Breakthrough Therapy designation in 2017. The FDA has 60 days to determine whether the NDA will be accepted for review and whether it will be a priority or standard review (six months or ten months, respectively). If approved by the FDA, the DEA will be required to reschedule MDMA making it available by prescription for medical use. The CEO of MAPS PBC said, “If approved, MDMA-assisted therapy would be the first psychedelic-assisted therapy, which we hope will drive additional investment into new research in mental health.”

Not everyone thinks FDA approval MDMA-assisted therapy is a good idea. The psychiatrist Allen Frances said the benefits in the active group were not much greater than the benefits in the placebo group. The cost of treatment would put it out of the reach of many potential patients, adding huge costs while providing only a small, benefit. Eric Turner, a former reviewer of psych drugs for the FDA, said he doubted the touted difference between MDMA and placebo groups was as big as it seems because the trials weren’t truly blinded. He didn’t think the MDMA trials met the FDA’s usual criteria for a well-controlled study.

The double-blind methodology in the Phase 3 Clinical trials was clearly ineffective and the dramatic results reported should be tempered with this in mind. The miniscule population size of participants for both trials also raised serious questions about an FDA approval. Phase 3 clinical trials are recommended to contain 300 to 3,000 participants by the FDA; the MAPS trials had 79 and 104 participants.

In Never Enough, Dr. Judith Grisel voiced her reservations with MDMA as a recreational or therapeutic drug. Grisel has a unique position as a neuroscientist and person in long-term addiction recovery. She said MDMA (ecstasy) is both a stimulant and a hallucinogen. Structurally, it fits better with the stimulants. “Amphetamine, methamphetamine and MDMA all acutely interact with monoamine transporters to block reuptake and cause release of dopamine, norepinephrine, and serotonin from nerve terminals.”

Ecstasy is not at all similar to LSD or psilocybin, though, and like that of other stimulants its ability to block reuptake of monoamines is what leads to enhanced energy, endurance, sociability, and sexual arousal, justifying its reputation as a perfect party drug.

It reaches peak concentration in the blood after two hours and has a half-life of about eight hours. Within an hour of taking MDMA, there is a huge increase in serotonin and other monoamines, followed by a reduction that develops over days as the drug is slowly metabolized. “As a result, people frequently experience aftereffects such as lethargy, depression, and memory or concentration problems” for a few days. Grisel acknowledged the acute effects make the short-term dip well worth it for some.

The drug greatly enhances a sense of wellbeing and produces extroversion and feelings of happiness and closeness to others, due in part to the fact that it impairs recognition of negative emotions, including sadness, anger, and fear. Affective neuroscience (the study of the brain’s role in moods and feelings) has demonstrated quite clearly that we can’t feel what we can’t recognize, so this pro-social bias seems perfectly engineered and helps explain why ecstasy is called the love drug and has been adopted for use by marriage counselors. In terms of unpleasant acute effects, the drug can cause overheating, teeth grinding, muscle stiffness, lack of appetite, and restless legs.

Grisel thought regular users were headed for a lifetime of depression and anxiety. Research in rats and primates suggests moderate to high doses of MDMA damages nerve terminals, perhaps permanently. “For example, primates given ecstasy twice a day for four days (eight total doses) show reductions in the number of serotonergic neurons seven years later.”

It seems MDMA causes non-repairable damage, especially to serotonergic neurons, leading to degeneration of axons and loss of connection between cells. These neurotoxic effects suggest that this drug is anything but innocuous. Though we’re not exactly sure how regular or semi-regular recreational use affects the human brain, because these studies would require autopsies (and control groups!), in my view it doesn’t look good. For instance, the extent of MDMA use in humans is positively correlated with the decrease in serotonergic function.

Grisel thought a study by Taurah, Chandler and Sanders published in Psychopharmacology should be read by everyone thinking of using the drug. The aim of their study was to see whether MDMA produced lasting effects on humans, as it did in animals. The loss of serotonin and norepinephrine function would be predicted to produce depression, impulsivity, and cognitive impairment “because serotonin transmission is so critically involved in mood, behavioral regulation, and thinking.” Their study included almost a thousand participants, about 20% who were drug naïve. The rest were equally divided among five groups of recreational drug users.

The researchers assessed a variety of measures including several associated with mood and cognition. There were two major findings. First, former and current ecstasy users were virtually identical, and second, these groups showed significantly more clinically relevant levels of depression, impulsiveness, poor sleep, and memory impairment. Again, these were recreational users, many had not had taken the drug for years, and still deficits were strikingly evident.

Grisel then related how her interactions with MDMA users matched the findings of Taurah, Chandler and Sanders. She described an encounter with a former undergraduate student, eager to gain research experience, who worked in her laboratory one summer. While he became less reliable as the weeks went on, she said he made up for it “by offering clever and insightful ideas about experimental design and interpretation, and when he was on, he was really very good.” She learned he worked as a DJ for local raves and told her that MDMA helped him “stay in the groove for the many hours of partying.”

The next summer he again applied to do research with her. While she wasn’t thrilled with the prospect, she remembered how undergraduate research experiences were significant in her own transition from a drug user to a drug researcher. “It didn’t go well. He was all over the place with his ideas, mads as many mistakes the first week as most newbies make in a semester, and couldn’t remember what we’d discussed from hour to hour, let alone day to day.” Grisel had to let him go, and when talking about the probable cause of his dramatic slip, he said it might be because he’d done “too much molly.”

I bumped into him a few years later while I was attending a scientific meeting in the same town which he worked as a bartender. More recently, I learned that a persistent state of chronic despair drove him to suicide.”

MAPS PBC changed its name to Lykos Therapeutics on January 5, 2024. This led to the FDA accepting Lykos Therapeutics’ New Drug Application (NDA) for MDMA-assisted therapy for PTSD on February 9, 2024. The FDA granted the application priority review and set a target action date of August 11, 2024 to make the review determination.

MAPS has been persistently and progressively chipping away at getting MDMA-assisted therapy approved to treat PTSD for many years. Let’s be careful to not release a so-called “treatment” that makes things worse for troubled people. For more on the concerns with FDA approval of MDMA-assisted therapy, see “Don’t Roll the Dice with MDMA.” For more information on concerns and reservations with psychedelics as the newest psychiatric craze, see Part 1 of this article.

04/9/24

Kingdom Now: Bringing Heaven to Earth

Photo by KNXRT on Unsplash

Do you attend a church that believes God always wants to heal, that the miraculous and supernatural should be a normal part of life and worship? Is your church structured to be led by the offices of apostles and prophets? Is it striving to establish the Kingdom of God on earth? If so, you are in one that is striving to follow Kingdom Now Theology.

These beliefs, God always want to heal, churches should be governed by apostles and prophets, and what I’ve called Kingdom Now theology are foundational to the NAR—the New Apostolic Reformation. C. Peter Wagner, a former professor at Fuller Theological Seminary, is credited with coining the term, New Apostolic Reformation. In Apostles Today, he said it was a reformation, “because we are witnessing the most radical change in the way of ‘doing church’ since the Protestant Reformation. It is ‘apostolic’ because the recognition of the gift and office of apostle is the most radical of a whole list of changes from the old wineskin” (p. 9). Then in Dominion! Your Role In Bringing Heaven to Earth, Wagner said: “The practical theology that best builds a foundation under social transformation is dominion theology, sometimes called ‘kingdom now’” (p. 59).

This so-called movement, the New Apostolic Reformation, attempts to clothe itself in doctrinal and hermeneutical systems that sound like orthodox “Christianity,” but are actually heterodoxy and dangerously close to heresy. In turn, we will examine these beliefs particularly as they are taught by Bethel Church of Redding California and its apostle/prophet leadership pair, Bill Johnson and Kris Vallotton. The research and work of Holly Pivec and Doug Geivett in Reckless Christianity, will guide our discussion here.

Johnson teaches that God’s goodness means it is always His will to heal a person; and this “truth” is now being restored to the church. It is the Christian’s assignment is to “bring heaven to earth.” He calls this the “cornerstone” of the church’s theology. In The Supernatural Power, Johnson said what is free to operate in heaven, should be free to operate here on this planet. And what is not free to operate there should not be free to operate here. “We are out to destroy the works of the devil.” Pivec and Geivett said:

In other words, there’s no sin, or sickness, or disease, or depression, or poverty in heaven. So, for heaven to come to earth means that none of those things should be found on earth either. And it isn’t merely that sin and suffering should not, ideally, exist in the world today. Rather, Christians have been tasked to make earth’s reality as unqualified reflection of heaven. As Johnson has said, ‘My assignment isn’t to go to heaven; my assignment is to bring heaven. . . . We’ve been given a mission and that mission is to pull on the reality of that world until it manifests in this one.’

In When Heaven Invades Earth, Johnson re-interprets the Lord’s Prayer (“Your kingdom come. Your will be done on earth as it is in heaven”) to mean if it exists in heaven, it is to be loosed on earth. He said this is the primary focus for all prayer. When the believer prays according to the revealed will of God, “faith is specific and focused. Faith grabs hold of that reality. Enduring faith doesn’t let go.” Supposedly this causes the circumstances here on earth to line up with heaven.

Conversely, if something does not exist in heaven, (death, sickness, poverty, addiction) it can be bound here through prayer, as we exercise the authority—the keys—given to us in Matthew 16:19. And yet his wife, Beni Johnson, died after a long battle with cancer. Despite the persistent exercise of that authority to release her healing.

Another one of the greater works that believers will bring back to earth is raising the dead. . .  except when they don’t. On December 14, 2019 a two-year-old girl named Olive stopped breathing and died in her sleep. Olive’s parents (her mother was a worship leader at Bethel), following the teaching of Bethel’s leaders, believed God would raise her from the dead. In Counterfeit Kingdom, Pivec and Geivett said: “Through social media, Bethel leaders urged Christians around the world to join the parents in ‘declaring’ a resurrection because they believed their spoken words, as children of God, had the power to bring Olive back.” After six days with no success, Bethel announced the family had begun to plan a memorial service.

Bill Johnson acknowledged that no one knows for sure how much of heaven God has purposed to become manifest here on earth—which would explain why his wife was not healed and why Olive was not raised from the dead. “But we do know through Church history that it’s more than we have now.” So, there is a Dead Raising Team that goes around to churches. Pivec and Geivett said this team has trained sixty other teams worldwide to go to the scenes of accidents, hospitals, and morgues to pray for resurrections. “They claim to have seen fifteen resurrections to date.” Even Kris Vallotton claimed there have been two “dead risings” reported by their online BSSM (Bethel School of Supernatural Ministry) school.

Bethel members also practice “grave soaking” or “grave sucking.” The purpose is to “soak” up a past miracle-worker’s anointing (i.e., Smith Wigglesworth, Kathryn Kuhlman). See this Grave Soaking – AG3 Teaser on Facebook or this video by a BSSM graduate and Bethel pastor at Smith Wigglesworth’s grave in England. Bethel leaders have denied they taught or encouraged the practice. Yet, Reckless Christianity and other easily obtained evidence, such as Facebook posts, photos and videos exist. “From an outsider’s perspective, Bethel responses to the allegations look like a coverup.”

Greater Works Than These

Bill Johnson and the NAR believe that the greater works promised to the disciples in John 14:12 are miracles. He said he looked forward to the day when the Church stands up and says, “Don’t believe us unless we are doing the works that Jesus did!” He said Jesus’ statement of us doing greater works than He did has stirred the church to look for some abstract meaning to a very simple statement. Greater means greater; and the works are signs and wonders. He then went on to say this understanding, was supported by the Greek of the verse.

In When Heaven Invades Earth Johnson said, “The word greater [in John 14:12] is mizon in the Greek. It is found 45 times in the New Testament. It is always used to describe ‘quality,’ not ‘quantity.’” But he misspelled meizon, as mizon. He doesn’t say where he got his information, but it seems he used an Enhanced Strong’s Lexicon to identify meizon:

3187 μείζων [meizon /mide·zone/] adj comparative. Irregular comparative of 3173; 45 occurrences; AV translates as “greater” 34 times, “greatest” nine times, “elder” once, and “more” once. 1 greater, larger, elder, stronger.

The standard Greek lexicon, BDAG, gives the meaning for the word translated “greater” in John 14:12 as: pertaining to being above standard in intensity, great.

Here is a link to Bible Hub for 3187, meizon: https://biblehub.com/greek/3187.htm

In the Theological Dictionary of the New Testament discussion of μέγας (megas, great) in John 14:12, the author referred first to John 5:19-21. Jesus said he could not do His miracles independent of the Father. He does what he sees the Father doing; what the Father shows the Son. He said it showed the unity of purpose between the Father and the Son. “And greater works than these will he show him, so that you may marvel. For as the Father raises the dead and gives them life, so also the Son gives life to whom he will.”

The great works that His disciples will do, ones greater than the miracles done by Jesus, is ζωοποιεῖν, being made alive. “Going to the Father [in John 14:12] gives Him the possibility of greater efficacy exercised through the disciples.” In other words, the greater works is the salvation of all those who the Son will raise to life, just as the Father raised Him. This is a greater thing when compared to the miracles that Christ performed. D.A. Carson said the following in his commentary about John 14:12:

The ‘signs’ and ‘works’ Jesus performed during his ministry could not fully accomplish their true end until after Jesus had risen from the dead and been exalted. Only at that point could they be seen for what they were. By contrast, the works believers are given to do through the power of the eschatological Spirit, after Jesus’ glorification, will be set in the framework of Jesus’ death and triumph, and will therefore more immediately and truly reveal the Son. Thus greater things is constrained by salvation-historical realities. In consequence many more converts will be gathered into the messianic community, the nascent church, than were drawn in during Jesus’ ministry.

Bill Johnson, again, distorts the meaning of Scripture in an attempt to support his theology. Johnson and the NAR are systematically deconstructing the theology and structure of the modern church, claiming that the “authentic gospel” or the “gospel of the kingdom” is always associated with signs and wonders: heal the sick, raise the dead, preach the gospel. “God’s goodness” means it is always God’s will to heal a person; a “truth” now being restored to the church. This is a radical departure from Scripture and not just a logical extension of charismatic, continuist belief. NAR and Johnson/Bethel Church assert a theology of the supernatural—of bringing heaven to earth—that goes beyond what the church and Scripture can claim is our mission.

This article was heavily influenced by the research and thought of Holly Pivec and R. Douglas Geivett and their books, Reckless Christianity, A New Apostolic Reformation? and Counterfeit Kingdom. Look for further articles on other aspects of “Kingdom Now.”

04/2/24

Is Indivior a Good Steward of Its Opioid Treatments?

Image by Лечение Наркомании from Pixabay

Fierce Pharma reported in 2020 that the former Indivior CEO was sentenced to six months in federal prison for his role in misleading officials about the supposed dangers of Suboxone tablets. He was also fined $100,000 and forfeited another $500,000. But it seems now he’d like to be a consultant to individuals or companies attempting to bring a new drug to market. However, the FDA rejected that plan for now. On February 27, 2023 he was debarred by the FDA for “5 years from providing services in any capacity to a person that has an approved or pending drug product application.” What was he involved in that resulted in his prison sentence and debarment by the FDA?

According to Fierce Pharma, on October 23rd, 2023, Indivior agreed to pay $385 million to settle lawsuits in the U.S. brought by drug wholesalers claiming it illegally suppressed generic competition for Suboxone. But that’s not all. The company also agreed in June of 2023 to pay $102.5 million to settle a 2016 lawsuit charging that Indivior’s actions when switching from a tablet to an oral film form version of Suboxone was done to extend its monopoly with Suboxone. AND in August of 2023, it offered $30 million to settle with health plans making similar claims. This was in addition to the $300 million Indivior paid in 2021 to resolve claims it “falsely and aggressively” marketed the drug, which led to the misuse of state Medicaid funds.

All this happened after Indivior was sued in 2020 by its former parent company, Reckitt Benckiser, seeking $1.34 billion in damages tied to its marketing scheme for Suboxone film. Then on December 20, 2023 Indivior announced that it had entered into a settlement agreement with Actavis Laboratories, a subsidiary of Teva Pharmaceuticals, to resolve patent disputes regarding Actavis’s Abbreviated New Drug Application (ANDA) for generic buprenorphine and naloxone sublingual film. Under the settlement, Actavis can launch the generic film products in ANDA no earlier than January 31, 2025.

It seems Indivior as a company is trying to leave its chaotic and costly past behind. In About Us, Indivior said it “is a global pharmaceutical company working to help change patients’ lives by pioneering life-transforming treatment for addiction and other serious mental illnesses.” Their vision is to provide access to evidence-based treatment to the millions of people across the globe who suffer from substance use and serious mental illness. They also say they take their role as a steward of their medications extremely seriously:

We cultivate a culture of integrity and commit ourselves to the highest standards of governance. We believe our long-term success is directly linked to operating in a responsible way and in a way that minimizes our impact on the environment. We support efforts to educate around safety and proper use of our medication-assisted treatments.

Origins of Indivior

In case you’re not familiar with the company, here is a brief history of Indivior from Wikipedia and “The Opioid Buzzard.” It was established as the buprenorphine division of Reckitt Benckiser in 1994. Suboxone and Subutex were approved for the treatment of opioid addiction in October of 2002. They were both sublingual (under the tongue) tablets. Suboxone consists of buprenorphine and naloxone; Subutex was just buprenorphine. They came to market in 2003.

In 2007 Reckitt Benkiser (RB) acquired the rights for the sublingual film version of Suboxone from MonoSol Rx. RB knew its patent exclusivity for Suboxone and Subutex would expire in 2009, so they submitted a New Drug Application for the film version of Suboxone, which was approved in August of 2010. In their 2011 annual report (no longer retrievable from its website), RB indicated to their shareholders that competition from generics could take up to 80% of the revenue and profit from the U.S. Suboxone market. But they expected “that the Suboxone film will help to mitigate the impact.”

In September of 2012 RB announced that they were voluntarily withdrawing Suboxone tablets from the market because of data they had received from the U.S. Poison Control Centers suggesting there were higher rates of pediatric overdose on the tablet formulation than the film version. They said they would take the tablet form off the market to “protect public health and safety.” The very same day RB filed a “Citizen’s Petition” with the FDA calling for the agency to postpone the approval of generic version of Suboxone in the interests of public safety. Subutex tablets were discontinued in 2011 and Suboxone tablets met the same fate in in 2012. For more on this action by RB, see “The Opioid Buzzard.”

In December 2014 Reckitt Benckiser made the buprenorphine division a separate company named Indivior. By February 2015, it was capitalized on the London Stock Exchange at $3.1 billion. And on April 9th 2019, a federal grand jury indicted Indivior for allegedly engaging in an illicit national scheme to promote Suboxone. See “The Pied Pipers of Suboxone” for more on this topic.

Indivior Products for Opioid Use Disorder

The Indivior products currently available in the U.S. to treat opioid use disorder include: Suboxone, a buprenorphine and naloxone sublingual film, Opvee, a nalmefene nasal spray for the emergency treatment of known or suspected overdose of opioids, and Sublocade, an extended-release injection of buprenorphine. Opvee and Sublocade are newer products than Soboxone and will be described below.

NPR noted Opvee was developed by Opiant Pharmaceuticals, which was acquired by Indivior in March of 2023. Opvee was approved by the FDA in May of 2023 and is similar to Narcan which contains naloxone. It apparently has a longer-acting effect than naloxone, which has some experts concerned. Nevertheless, Nora Volkow, the director of the National Institute on Drug Abuse, said: “The whole aim of this was to have a medication that would last longer but also reach into the brain very rapidly.”

An adverse side effect of opioid reversal drugs like Narcan and Opvee is they create intense withdrawal symptoms including: nausea, diarrhea, muscle cramps, anxiety, restlessness or irritability, increased blood pressure, rapid heart rate, body aches, and others. Important Safety Information for Opvee cautioned that the use of Opvee (leading to abrupt postoperative reversal of opioid depression) “may result in adverse cardiovascular effects” in people with preexisting CV disorders. So, these patients should be closely monitored in a healthcare setting. And it warns that some patients may become aggressive when an opioid overdose is reversed (treated) with Opvee.

With naloxone (Narcan), these symptoms could last 30 or 40 minutes. With Opvee (nalmefene) they can last six hours or more, “requiring extra treatment and management by health professionals.” GoodRx Health said: Opvee’s half-life is about 11 hours, while Narcan’s half-life is about 2 hours. Read between the lines here. A person uses opioids to experience the high or euphoria AND to avoid withdrawal. So Opvee immediately blocks the high and brings on withdrawal. It extends the withdrawal symptoms to six hours or more, with the potential of the treated person wanting nothing less than to find more opioids to cope with the withdrawal and driving them to use a higher dose of opioids to overcome the nalmefene—with the potential of adverse cardiovascular effects in people with preexisting CV disorders.

If this “treatment” occurs, as is likely, outside of a healthcare facility, the person or persons who administered the Opvee will have to convince person to go to an emergency department or other healthcare facility. There is a better chance of success if the withdrawal symptoms only last 30 or 40 minutes than six hours or more. No wonder some individuals get aggressive when treated with Opvee. Should it be limited to use with overdose victims who are already in a healthcare facility or by emergency responders like EMT or police?

Dr. Lewis Nelson of Rutgers University, a former advisor to the FDA, said the risk of long-lasting withdrawal is something they try to avoid. He added a second or third dose of naloxone is easy enough to give and works perfectly well.

Indivior said it is still considering what to charge for its drug. It will compete in the same market as naloxone, where most buyers are local governments and community groups that distribute to first responders and those at risk of overdose. Indivior has told investors that Opvee could eventually generate annual sales between $150 million to $250 million.

Sublocade was approved by the FDA in November of 2017. It is a monthly injection of buprenorphine to treat individuals with moderate to severe opioid use disorder. “It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days.” It is a drug-device combination product that is injected under the skin (subcutaneously) as a solution, but forms a solid deposit or depot of buprenorphine. After the initial formation of the depot, buprenorphine is released as the depot biodegrades.

The monthly injection of buprenorphine in Sublocade is another treatment option for opioid use disorder (OUD). It has the advantage of gradually releasing buprenorphine at a controlled rate, meaning that the levels of buprenorphine stay consistent in the blood throughout the month. In a study reported on in the above-linked description on how Sublocade works, Indivior provided a chart illustrating how buprenorphine levels were delivered at sustained levels, after a required preliminary period of daily oral buprenorphine for at least 7 days to control withdrawal symptoms. The required daily use of oral buprenorphine helps assure the healthcare provider the person did in fact stop their use of opioids before they began their daily use of Suboxone because buprenorphine acts as a partial antagonist, blocking the ability of many opioids to cause an effect.

Should the person decide to stop taking Sublocade, the terminal half-life of Sublocade is 43 to 60 days. According to Drugs.com, it usually takes four to five half-lives for a drug to be totally eliminated from the body. So, no trace of buprenorphine from Sublocade should be found after 172 to 300 days. This raises the potential use of Sublocade as a tool for slow tapering once the individual has reached a steady-state (4-6 months), instead of treatment with Sublocade continuing indefinitely.

A Slow Buprenorphine Taper with Sublocade?

Dr. Leeds, a Suboxone doctor in Fort Lauderdale FL, described just such a way Sublocade could be used to taper off Suboxone. He said many patients often want to know from their first visit to a Suboxone doctor if there is a way to eventually get off Suboxone. Their reason is the buprenorphine in Suboxone is an opioid drug and causes physical dependence like all opioids. If a patient taking Suboxone quits treatment early, they will develop withdrawal symptoms. A gradual taper is the solution to minimize the physical opioid withdrawal symptoms.

However, the medication is not well-designed for a taper. Doctors who help their patients with tapering off Suboxone quickly realize that the Suboxone sublingual films are not available in enough dosage increments to all for proper gradual tapering.

In order to avoid serious withdrawal symptoms, a patient most often must reduce their dosage gradually, to the lowest dose possible, such as buprenorphine 0.25mg daily, or even less. Unfortunately, the lowest Suboxone dose is 2mg.

Additionally, the manufacturer, in the Suboxone prescribing information, states that patients should not cut or split the tablets or films. Suboxone makers are clearly not interested in helping patients with tapering off Suboxone.

Dr. Leeds noted that since the subcutaneous buprenorphine shot takes many months to fully wear off, “it does seem possible that it might help some patients with the tapering process.” However, the buprenorphine taper would be off-label and experimental at this point. There would be no available guidance from experts, “because Sublocade has not been widely used for Suboxone tapering.”

For the present, he does not recommend finding a doctor willing to use Sublocade to taper off Suboxone. But he encouraged interested people to reach out to researchers and research centers in the field of opioid use disorder treatment. “If Suboxone scientists are aware that people are interested in this research, they might decide to seek funding for such studies.” He also suggested there may be doctors who are using Sublocade off-label for Suboxone tapering, who may have anecdotal information to help other interested doctors.

Drugmakers are quick to recommend that doctors get their patients onto their medications. Yet, they do little to guide doctors in getting patients off of these meds when treatment has been completed.

Are you listening, Indivior? You describe yourself as “a global pharmaceutical company working to change patients’ lives by pioneering life-transforming treatment for addiction.” You further said you believed your “long-term success was directly linked to operating in a responsible way.” Is it responsible to neglect to provide guidance for individuals who would like to taper off their use of Suboxone and Sublocade, which are opioids—meaning they make their users physically dependent on them. Does the safe and proper use of your medication-assisted treatments require you to ignore those who want a safe and proper method of tapering off of them?

If you truly take the stewardship of your medications extremely seriously, shouldn’t you be willing to fund research into Suboxone tapering with Sublocade?

03/26/24

What the Book of Job Does

John Walton opens Lecture 15 on Job by noting Job 19:25 is one of the most familiar verses in the book of Job. The NIV (the ESV is similar) says, “I know that my Redeemer lives, and that in the end he will stand upon the earth.” This verse has inspired musicians from Handel to Nicole C. Mullen. It has been traditionally understood by Christians including Clement of Rome, Origen and Augustine to refer to the resurrection and Christ. In “Impatient Job,” James Zink observed that most commentators see in Job 19:25-27, “the height of trust in the justice of God and a great new insight into his redemptive nature.” And yet Walton provocatively asked, “So, how should we interpret this verse?”

Walton said we should remember that Hebrew doesn’t have capital letters, meaning that the capitalizing “Redeemer” in the NIV, ESV and other translations for Job 19:25 is interpretation. He goes on to say it needs to be understood in relationship to the Job’s many previous references to an advocate related to his legal case. “He’s looking for someone to represent him before God; someone who will take his case,” who will advocate for him. There are a number of words used by Job to refer to this position, but they all focus on the same kind of role as someone who will be his advocate before God. “Now we have to ask the question, ‘What sort of advocate does Job seek and who does he expect to fill that role?’”

The word translated as redeemer here in Job 19:25 is goʾel. Job desires an advocate or mediator to come to his aid. He wants a goʾel (redeemer) to demonstrate that he is innocent. He is convinced he has not done anything that deserves the treatment he has received. “He’s not looking for someone to save him from offenses;” that’s not what a goʾel does. “He wants it on record, that he did nothing to deserve his suffering.”

Walton observed this was not the redeemer role of Jesus. He added that no New Testament writer drew an association between Jesus and Job 19. In the Theological Wordbook of the Old Testament, R. Laird Harris said goʾel more accurately referred to the work of God “who as a friend and kinsman through faith will ultimately redeem Job from the dust of death.” If the author of Job intended to refer to the coming of Christ in his work of atonement, “This would be expressed more characteristically by the Hebrew word pādâ,” instead of goʾel in 19:25. Walton said of Job:

He feels like a wrong has been done to him. A goʾel does not work on behalf to right a wrong the person has committed. That’s what Jesus did, but that’s really not the role we find of a goʾel here. Job wants an advocate here, a goʾel and redeemer, who will demonstrate that he is innocent. He’s not looking for someone to save him from the offense he’s committed. He’s persuaded he has not committed anything that deserves the treatment he has gotten. He’s not looking for someone to save him from offenses.

Walton thought Job expects his goʾel to arrive and testify at his grave, in other words, after his death (19:26). He said there are three major theories for understanding when the goʾel will appear in relation to his death. The one traditionally seen in church history by Clement, Origen, Jerome and Luther was that God will raise him up from the grave. But this contradicts Job’s earlier affirmations of the permanency of the grave (See Job 14). Furthermore, according to Walton, resurrection was not part of Israelite doctrine throughout most of the Old Testament.

Others think Job expects a “posthumous vindication.” After he’s gone, somehow Job will be vindicated. But Walton tends to think Job believes there will be a last-minute reprieve. God will intervene and vindicate him before he dies. Where Job said: “after my skin has been destroyed” in verse 19:26, he was referring to scraping off his skin (Job 2:8), as he scraped himself with a potsherd. “Yet in my flesh I shall see God.”

Walton said this means Job believed he would be restored to God’s favor. Even if he scraped away all his skin (a hyperbole), “He will see God’s restoration in the flesh” before he dies. “Job has no hope of heaven. Seeing God refers to being restored to favor, and that he’ll no longer be a stranger, an outsider, out of favor.” He than gave this expanded paraphrase of Job 19:25-26:

I firmly believe that there is someone (perhaps from the divine council), somewhere, who will come and testify on my behalf right here on my dung heap at the end of all this. Despite my peeling skin, I expect to have enough left to come before God in my own flesh. I will be restored to his favor and no longer be treated as a stranger. This is my deepest desire!” (prosperity has nothing to do with it).

Walton said this was a significant affirmation on Job’s part. And you miss it entirely when you try to make Jesus the redeemer. “Jesus is our Redeemer, but he’s not the kind of redeemer Job is looking for here.” He wasn’t looking for someone who would take the punishment for his offenses and justify him. He was looking for vindication, not justification—which was not something Jesus provided. “Job is expecting someone to play a role that is the polar opposite of that which is played by Jesus.”

Viewing Jesus as the goʾel in Job is a distorting factor in the interpretation of the book and runs against the grain of Job’s hope and desire. Jesus is not the answer to the problems posed in the book of Job; though he is the answer to the larger problem of sin and the brokenness of the world. The death and resurrection of Jesus mediate for our sin, but do not provide the answer for why there is suffering in the world or how we should think about God when life goes wrong. That’s what the book of Job does.

02/6/24

Psychedelics as the Newest Psychiatric Craze, Part 1

pixabay.com

In October California Governor Gavin Newsom vetoed a bill that would have decriminalized the possession and personal use of several plant-based hallucinogens, including psilocybin, mescaline and dimethyltryptamine (DMT), saying more work needed to be done on treatment guidelines. The legislation would have decriminalized possession before setting up regulatory treatment guidelines, with the California Health and Human Services Agency supposed to make recommendations to lawmakers after the consequences of decriminalization. The bill would not have arrested or prosecuted individuals who possessed limited amounts of plant-based hallucinogens. Also, the bill did not legalize the sale of these psychedelics. They are still illegal under federal law.

Public opinion was said to have shifted on using psychedelics to treat trauma and other disorders such as depression, and alcohol use disorder. There has been a significant amount of interest in the potential of psychedelics for mental health that includes encouragement and discouragement of treating psychiatric conditions with them. Sandy Cohen opened her article “Do psychedelics have a role in psychiatric treatment?” for UCLA Health, with the provocative question, “What if there was a medication that could significantly reduce symptoms of treatment-resistant depression in a single dose?” A UCLA Health psychiatrist, Walter Dunn, described two studies where psilocybin was found to have a significant reduction in symptoms of treatment-resistant depression. He said these results were unprecedented: “We have nothing that works this well.”

Dunn said the coverage in mainstream media and books aimed at lay audiences (such as Michael Pollan’s book, How to Change Your Mind) have raised interest and curiosity in psychedelics. He said when he goes to dinner parties and people discover his work is with psychedelic drugs, “I’m talking about them for the rest of the evening.” According to a UC Berkeley Psychedelics Survey, 61% of registered American voters support legalizing regulated therapeutic access to psychedelics. Thirty-five percent of those supporters said they strongly support such action. But there were 35% who opposed it and 69% did not see it as something “for people like me.”

We are in a historic moment in the space for psychedelic science, research and also mental health in general. . . There hasn’t been any time in modern psychiatry where there has been so much interest, awareness and discussion around a potential mental health treatment.

Dunn acknowledged the drugs come with risks, which was one of the reasons the FDA has been cautious about the trials being run. “These are not benign medicines. Anything that can help you can harm you.” He discussed how the FDA was set to consider MDMA-assisted therapy for PTSD in 2024. It’s still unclear whether or not the FDA will want a Risk Evaluation and Mitigation Strategy (REMS), if these treatments are approved. A REMS could require psychedelic-assisted therapy to included two specially trained and certified clinicians during the psychedelic experience. If a REMS is required by the FDA for MDMA-assisted therapy, it would reduce the pool of therapists who could administer the treatment and decrease access even as it enhances safety.

Joanna Moncrieff, a British psychiatrist, noted in “Psychedelics—The New Psychiatric Craze” where they were viewed as an increasingly fashionable medical treatment. But she wondered if they had any objective health benefits and were they safe. She noted where psilocybin, LSD, MDMA and ketamine were some of the psychedelics being recommended for an ever-lengthening list of problems that include depression, anxiety, addiction, and PTSD. She acknowledged some people might learn important about themselves through the effects of psychedelic drugs.

But these benefits are not medical or health effects. They are akin to the personal development people achieve through other sorts of activities and life experiences. . . And although the concept of drug-assisted psychotherapy acknowledges that it is the way the psychoactive effects of the drugs are used to promote a process of personal learning that is relevant, why not employ other, safer and cheaper methods? Why not nature-assisted psychotherapy (a walk in the park), for example?

Yet, the use of these drugs is portrayed as if they work by targeting underlying dysfunctional brain processes. Moncrieff is concerned that when psychedelics get a medical license, psychotherapy will be dropped or minimized. “As with ketamine, the tendency of all psychedelic treatment will be towards the provision of the drug in the cheapest possible way, which means the minimum of supervision and therapy.” Presciently, Moncrieff wrote her article two years ago, before the accidental death of Matthew Perry from the acute effects of unsupervised ketamine use.

She said most psychedelic research ignores the way the immediate psychoactive effects of the drugs impact people’s feelings and behavior in a way that will influence mood symptom ratings and may produce the impression of improvement.  She singled out the American Psychiatric Association’s report on ketamine treatment, which said there was compelling evidence the antidepressant effects of ketamine infusion are rapid and robust. While the APA acknowledged the antidepressant effects were transitory, they did not explain how they could be distinguished from the euphoria and other mental alterations associated with acute ketamine intoxication. “If ketamine’s effects are ‘antidepressant’ then so are the effects of all the other drugs that produce short-term euphoria including alcohol, cocaine, heroin, amphetamines, etc.”

Any powerful mind-altering drug will likely have ‘placebo’ effects. Drug-induced experience will lead people to expect they will improve or think they have improved. Psychedelic research also neglects the hours of medical supervision and professional attention associated with psychedelic treatment. Clinical contact improves people’s outcomes in depression, as was seen in esketamine trials, where a high level of professional contact seems to have exerted a powerful effect on some people.

The current craze for psychedelics also means the adverse effects are being minimised or overlooked. The ‘bad trip’ is a well-recognised phenomenon, and may not be that uncommon. Psychiatrist Rick Strassman, author of DMT: the Spirit Molecule, described how half of the 60 volunteers he injected with the powerful hallucinogen, DMT (N,N-dimethyltryptamine), experienced terrifying hallucinations and anxiety, and he discontinued his research, in part because of these effects. Science journalist John Horgan describes months of depression and flashbacks following a ‘bad trip’, and also reminds us that Albert Hofmann, who first synthesised LSD, also had doubts about it, calling his 1981 memoir LSD: My problem child.

Moncrieff ended her article by noting that while one or two doses of any drug is unlikely to do much harm, the tendency for treating mental health concerns is for long-term use. And repeated use of psychedelics is unlikely to be completely harmless. “As with so many other medical treatments, they have become popular through the potent mixture of financial interests and desperation.” There are many safer routes to promote personal development through an unusual experience. But we will be faced with a decision to legalize psychedelic-assisted treatment sooner rather than later, as MDMA-assisted therapy is expected to be submitted to the FDA for review for approval in early 2024. See Part 2 of this article for more information on the approval process for MDMA-assisted therapy.

01/30/24

Continue to Keep Marijuana Medical in PA

Photo by Alesia Kozik: https://www.pexels.com/

Medical marijuana has been available in Pennsylvania since February of 2018. Fortunately, progress to the legalization of recreational marijuana has not occurred yet. I’ve been urging for almost six years that we wait for the research into the risks and benefits of marijuana use can be reliably researched. Here are three recently published research articles to reflect on that suggest going ‘full Colorado’ in Pennsylvania may not be a good idea.

In August of 2023, The British Medical Journal (BMJ) published “Balancing risks and benefits of cannabis use” by Solmi et al. Their research was an umbrella review of 101 meta-analyses that have reported on the safety of cannabis, cannabinoids or cannabis-based medicines. According to the 2019 Global Burden of Disease Study, Solmi et al said more than 23.8 million people have cannabis use disorder (CUD). In the U.S., the prevalence of CUD was estimated at around 6.3% in a lifetime. In Europe, around 15% of people aged 15 to 35 reported using cannabis in the past year.

In Europe, over the past decade, self-reported use of cannabis within the past month has increased by almost 25% in people aged 15-34 years, and more than 80% in people who are 55-64 years. Cannabis or products containing tetrahydrocannabinol (cannabinoids) are widely available and have increasingly high tetrahydrocannabinol content. For instance, in Europe, tetrahydrocannabinol content increased from 6.9% to 10.6% from 2010 to 2019. Evidence has suggested that cannabis may be harmful, for mental and physical health, as well as driving safety, across observational studies but also in experimental settings. Conversely, more than a decade ago, cannabidiol was proposed as a candidate drug for the treatment of neurological disorders such as treatment-resistant childhood epilepsy. Furthermore, it has been proposed that this substance might be useful for anxiety and sleep disorders, and even as an adjuvant treatment for psychosis. Moreover, cannabis-based medications (ie, medications that contain cannabis components) have been investigated as putative treatments for several different conditions and symptoms.

There was converging evidence of an increased risk of psychosis in adolescents and adults, and with psychosis relapse in people with a psychotic disorder. There was an association between cannabis and general psychiatric symptoms such as depression and mania; and detrimental effects on memory, verbal delayed recall, verbal learning and visual immediate recall. “Across different clinical and non-clinical populations, observational evidence suggests an association between cannabis use and motor vehicle accidents.” There was also evidence of an association with somnolence (drowsiness) with cannabinoids and cannabidiol. Cannabis-based medicines were associated with visual impairment, disorientation, dizziness, sedation and vertigo.

In addition to the association of cannabis and psychosis, cannabis use is associated with a worse outcome after onset, including poorer cognition, lower adherence to antipsychotics and a higher risk of relapse. “In other words, use of cannabis when no psychotic disorder has already occurred increases the risk of its onset, and using cannabis after its onset, worsens clinical outcomes.” Mood disorders have their peak of onset close to that for cannabis use, raising concern because of the associations noted in this study between cannabis and depression, mania and suicide attempt. High THC content cannabis is thought to serve at a gateway to other substances, especially in younger people.

With regard to the therapeutic potential of cannabis-based medicines, cannabidiol was beneficial in reducing seizures in certain forms of epilepsy. They were also beneficial for pain and spasticity in multiple sclerosis, as well as for chronic pain in various conditions. In patients with chronic pain, the effects of prolonged use of cannabinoids needs to be tested “because current findings only come from short term randomized controlled trials.” Active comparisons between cannabidiol and available options for epilepsy, cannabis-based medicines and other pain medications, other treatments for muscle spasticity in multiple sclerosis are needed with a focus on efficacy and safety to inform future guidelines.

In conclusion, Solmi et al said converging and convincing evidence supported the association of marijuana use with poor mental health and cognition and the increased risk of car crashes. Cannabis use should be avoided in adolescents and young adults when neurodevelopment is still occurring, when mental health disorders begin and cognition is important for optimizing academic performance and learning. Cannabidiol could be considered as a potential treatment option in epilepsy. Cannabis-based medicines could be considered for chronic pain across different conditions, and for nausea and vomiting and for sleep in cancer.

Law and public health policy makers and researchers should consider this evidence synthesis when making policy decisions on cannabinoids use regulation, and when planning a future epidemiological or experimental research agenda, with particular attention to the tetrahydrocannabinol content of cannabinoids. Future guidelines are needed to translate current findings into clinical practice.

The 2022 National Survey on Drug Use and Health (NSDUH) released in November of 2023, 22% of people 12 or older reported using marijuana in various ways (smoking, vaping, dabbing, eating or drinking, lotion or cream, taking pills or some other way). The percentage was highest among young adults, 18 to 25 (38.2% or 13.3 million people), followed by adults over 26 (20.6%, 45.7 million people), then adolescents 12 to 17 (11.5%, 2.9 million people). Among people 12 or older in 2022, 6.7% or 19 million people, has a CUD (cannabis use disorder) in the past year. The percentage of young adults 18 to 25 with CUD was 16.5% or 5.7 million people. Adolescents aged 12 to 17 with CUD was 5.1%, or 1.3 million people. These figures were higher than the data reported in the following article, “Cannabis-Related Disorders and toxic Effects,” perhaps reflecting more recent data.

In December on 2023, The New England Journal of Medicine published “Cannabis-Related Disorders and Toxic Effects” by Daniel Gorelick. The article reviewed the seven cannabis-related disorders defined in the DSM-5-TR. The author said worldwide, an estimated 209 million persons between 15 and 64 used cannabis in 2020. In the U.S., an estimated 52.4 million people 12 and older used cannabis in 2021, representing 18.7% of that age group. And 16.2 million persons met the diagnostic criteria for CUD.

Cannabis use disorder occurs in all age groups but is primarily a disease of young adults. The median age at onset is 22 years (interquartile range, 19 to 29). In the United States, the percentage of 18-to-25-year-old persons with current (past-year) cannabis use disorder in 2021 was 14.4%. Younger age at initiation of cannabis use is associated with faster development of cannabis use disorder and more severe cannabis use disorder.

The major risk factors for developing CUD are the frequency and duration of cannabis use. And the core feature is loss of control, reflected in persistent use despite adverse consequences. The potency and amount of cannabis are also risk factors, but they have not been well studied because of the difficulty in quantifying the amount and potency of the THC content of products. “The potency of cannabis has doubled over the past 2 decades, according to analyses of samples seized by U.S. law enforcement, which may contribute to the increased risk of cannabis use disorder and cannabis-induced psychosis.” The risk of CUD increases with the frequency of use: 3.5% prevalence of CUD with yearly use (less than 12 days per year); 8.0% with monthly use (up to 4 days per month); 16.8% with weekly use (up to 5 days per week); and 36% with daily or near daily use.

Several clinical and sociodemographic factors are associated with an increased risk of cannabis use disorder, including the use of other psychoactive substances such as alcohol and tobacco; having had adverse childhood experiences (such as physical, emotional, or sexual abuse); having a history of a psychiatric disorder or conduct problems as a child or adolescent; depressed mood, anxiety, or abnormal regulation of negative mood; stressful life events (such as job loss, financial difficulties, and divorce); and parental cannabis use. These significant associations do not necessarily indicate a direct causal influence on cannabis use disorder, because many of these factors are also highly associated with both cannabis use and frequent cannabis use.

Gorelick told Medical Xpress almost 50% of people with CUD have another diagnosable psychiatric disorder such as major depression, PTSD or generalized anxiety disorder. He said: “There is a lot of misinformation in the public sphere about cannabis and its effects on psychological health with many assuming that this drug is safe to use with no side effects.” About 1 in 10 people who use cannabis will become addicted and if you start using before the age of 18 the risk rises to one in six. Cannabis use accounts for 10% of all drug-related emergency room visits and is associated with a 30 to 40 percent increased risk of car accidents.

He concluded that CUD and heavy or long-term cannabis use have clear adverse effects on physical and psychological health. He thought research on the endocannabinoid system is needed to better explain the pathophysiology of these effects and to develop treatments. In other words, continue to keep marijuana medical in PA until we have reliable research to determine whether or not recreational marijuana should be legalized. So far, it’s not looking to be a wise move.

For more information on marijuana and the concerns with legalization, search for “marijuana” or “cannabis” on this website or see, PREPARING to Legalize Cannabis.” For more information on marijuana legalization in Pennsylvania, see “Keep Marijuana Medical in PA,” “Waiting Before Pennsylvania Goes ‘Full Colorado’” and others.

01/23/24

Life, Liberty, and the Pursuit of Christian Nationalism

Image by 1778011 from Pixabay

After reading Paul Miller’s book, The Religion of American Greatness, I became aware of the problems of thinking of America as a “Christian Nation.” Simply put, it is a political ideology with a Christian gloss. I was relatively unaware of Christian nationalism until then, but was persuaded by his arguments. He wrote an article for Christianity Today, “What Is Christian Nationalism” where he noted that many of the rioters on January 6th, 2021 had Christian signs, slogans or symbols. “But none of this should be confused with the Christian’s identity in the transnational family of God, and no national political agenda or ideal can take priority over God’s global mandate and mission for his people.” It takes the name of Christ as a fig leaf to cover its political program, “treating the message of Jesus as a tool of political propaganda and the church as the handmaiden and cheerleader of the state.”

As Miller noted in his article, the term “Christian Nationalism” is a relatively new term, one which it seems many Americans are not familiar with. Slate said the term was “in the air” after January 6th rioters came to the Capitol waving Christian symbols and banners. But it has been embraced by others, including Marjorie Taylor Greene. She even hocked a Proud Christian Nationalist tee shirt in her Official MTG Shop. She also posted on X, formerly known as Twitter, that she was honored to meet Jake Chansley, the infamous QAnon shaman from January 6th.

The Pew Research Center also noted growing numbers of Americans were embracing the Christian Nationalist label, while others still saw it as a danger. Pew said their survey found most American adults believed the founding fathers intended the country to be a Christian nation (60%), with many affirming (45%) it should be a Christian nation today. When the survey’s respondents were separated into those who think the U.S. should be a Christian nation and those who did not, some interesting difference emerged. Among those who thought the U.S. should be a Christian nation, only 28% thought the country should openly declare it. Fifty-two percent thought no religion should be the official religion of the country.

Among those who thought the U.S. should not be a Christian nation, 1% thought the U.S should openly declare it, and 88% rejected the idea. Similar differences were found with whether the state should advocate for Christian religious values, or moral value shared by people of many faiths. And whether or not to enforce or stop enforcing the separation of church and state. See the Pew link for a graphic. Those who want the U.S. to be a Christian nation tended to want the Bible to have a great deal or some influence on U.S. laws (78%), while those opposed to the idea soundly rejected the idea (79%). See the chart below, found in the Pew article.

The Pew survey results disturbingly resonate with what Paul Schreiner called the “bad form” of Christian nationalism. This is a fusion of Christianity and civil life, where instead of persuasion, adherents seek to enact and enforce laws. This is attempting to bring about the kingdom of God by power and command, not by the Spirit of God. Schreiner acknowledged the distinctly Christian history of America, but noted how this sense of Christian nationalism goes against key features of the American experiment, namely pluralism and religious liberty.

Eliminating all dissent might sound attractive, and it certainly would allow governing authorities to get things done more quickly. But squashing dissent violates human liberty, equality, and the vision of the founding fathers. It requires coercion of and change from those who dissent. If taken to its logical conclusion, this Nationalism undermines the foundation of a free society. Should such a fusion dominate American civil life, it would divide the nation rather than unify it. Uniformity in some aspects of national life isn’t all bad, but that must always exist beside diversity.

See “What’s Wrong with Christian Nationalism?” or Paul Schreiner’s article, “The Good, the Bad, and the Ugly of Christian Nationalism” for a more through critique and discussion of this point.

Perhaps many of the Pew survey participants didn’t have a well-thought-out understanding of the nuances within so-called “Christian nationalism.” This seems to have been the case. Half of the Pew survey respondents were asked if they have heard the term “Christian nationalism.” Overall, 54% of Americans said they had never heard it. Non-Christians tended to be more familiar with the term (55%). But atheists (78%) and agnostics (63%) were most familiar. See the table below, found in the Pew article.

Schreiner warned that the “bad” form of Christian Nationalism becomes “ugly” when it “idealizes and advocates for a fusion of Christianity with American life and does so by dominion. This is the type of Christian Nationalism exhibited by some on January 6.” This conflates God and country, confusing the categories of Christian faith and nation-state and advocates for its goals by force or violence when deemed necessary. “No nation-state can be a Christian nation-state, because Christianity doesn’t work that way.” Here, the fig leaf referred to in the opening paragraph comes off and Christian nationalism is exposed as a political program of nationalism.

Jake Chansley, the infamous QAnon shaman from January 6th was sentenced and imprisoned for 27 months. At his parole hearing, he expressed remorse for his actions and said he no longer wanted to be known as the QAon Shaman, saying he was wrong to enter the Capitol . He was released into a Phoenix halfway house for ex-offenders. Seemingly unrepentant for his actions, he is now running for Congress in the state of Arizona as a Libertarian and has again embraced his role as the QAnon Shaman. Look at the link to “X” above where Marjorie Taylor Greene said she was honored to meet him. Also see his own Twitter feed.

In “What Is Christian Nationalism?” Paul Miller distinguished between Christian nationalism and nationalism. Miller said nationalism is the belief that humanity is divisible into mutually distinct culture group defined by shared language, religion, ethnicity, or culture. They should have their own governments; the governments should promote and protect a nation’s cultural identity. Sovereign national groups then provide meaning and purpose for human beings.

The problem is, humanity is not easily divisible into mutually distinct cultural groups. “Cultures overlap and their borders are fuzzy.” They make a poor fit as the foundation for political order. Whereas cultural identities are fluid and hard to draw boundaries around, political boundaries are hard and semipermanent. “Cultural pluralism is essentially inevitable in every nation.” Attempts to found political legitimacy on cultural likeness means the political order will consistently be felt to be illegitimate by some group.

In the absence of moral authority, nationalists can only hope to establish themselves by force. “Scholars are almost unanimous that nationalist governments tend to become authoritarian and oppressive in practice.” Miller observed that when Protestantism was a “quasi-official religion” in the U.S., “it did not respect true religious freedom.” Christianity was also used by the U.S. and many individual states to support slavery and segregation.

Miller thought Christian nationalism was the belief that the American nation is defined by Christianity; and the government should take steps to keep it that way and continue to be so in the future—to promote a specific cultural template as the “official” culture of the country. There may be some who want an amendment to the Constitution to recognize America’s Christian heritage. They strive to enshrine a Christian nationalist interpretation of American history in school curricula; that America has a special relationship with God; that it was chosen by him to carry out a special mission on earth. Others advocate for immigration restrictions to prevent changes to American ethnic demographics or a change to American culture. Others want to empower the government to take stronger action against immoral behavior.

Christian nationalism tends to treat other Americans as second-class citizens. If it were fully implemented, it would not respect the full religious liberty of all Americans. Empowering the state through “morals legislation” to regulate conduct always carries the risk of overreaching, setting a bad precedent, and creating governing powers that could be used later be used against Christians. Additionally, Christian nationalism is an ideology held overwhelmingly by white Americans, and it thus tends to exacerbate racial and ethnic cleavages. In recent years, the movement has grown increasingly characterized by fear and by a belief that Christians are victims of persecution. Some are beginning to argue that American Christians need to prepare to fight, physically, to preserve America’s identity, an argument that played into the January 6 riot.

Christianity is a religion focused on the person and work of Jesus Christ as defined by the Christian Bible and the Apostles’ and Nicene Creeds. It is the gathering of people “from every nation and tribe and people and language,” who worship Jesus (Revelation 7:9), a faith that unites Jews and Greeks, Americans and non-Americans together. Christianity is political, in the sense that its adherents have always understood their faith to challenge, affect, and transcend their worldly loyalties—but there is no single view on what political implications flow from Christian faith other than that we should “fear God, honor the king” (1 Peter 2:17), pay our taxes, love our neighbors, and seek justice.

Miller said normal Christian political engagement is humble, loving and sacrificial. It rejects the idea that Christians are entitled to primacy of place in the public square or that Christians have a presumptive right to continue their historical predominance in American culture. Christians should seek to love their neighbors by pursuing justice in the public square, which includes working against abortion, promoting religious liberty, furthering racial justice, protecting the rule of law, and honoring constitutional processes. “That agenda is different from promoting Christian culture, Western heritage, or Anglo-Protestant values.”

There is a “good” sense of Christian Nationalism, meaning simply that “Christianity has influenced and should continue to influence the nation.” The Declaration of Independence affirmed that all men (and women) are created equal. They are endowed “by their Creator with certain unalienable rights, that among these are life, liberty, and the pursuit of happiness.” Schreiner noted that such a principle was worthy of Christian advocacy alongside biblical views of marriage, sexuality, and abortion. “Our nation would be improved by affirming the goodness of natural law principles.”

In the best sense, this form of Christian Nationalism doesn’t attempt to dominate the political process or to make the nation completely Christian but seeks instead to bring change by persuasion. Rather than trying to overthrow the government, adherents advocate their cause by supporting laws, electing candidates, podcasting, writing, and developing think tanks. They won’t force their opinions, but they also won’t back down from arguing for them.

For further reflections on nationalism, see the link “Christian Nationalism” on this website.

01/16/24

Doubling Down on STAR*D Outcomes

Image by 2541163 from Pixabay

In January of 2006, the NIMH announced the results of Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study, the largest and longest study ever done to evaluate depression treatment. Its purpose was to determine the effectiveness of different treatments for people with Major Depression Disorder (MDD) who did not respond initial treatment with an antidepressant. The startling STAR*D results reported that almost 70 percent of those who did not withdraw from the study became symptom-free. “For the first time, doctors and people with depression now have extensive data on antidepressant treatments from a federally funded, large-scale, long-term study directly comparing treatment strategies.” However, the true remission rate turned out to be 35%, around half of what was reported.

In August of 2023 Ed Pigott and other researchers reanalyzed and published the patient-level data set from the STAR*D study in the British Medical Journal (BMJ), keeping their analysis to the original research protocol. They discovered the STAR*D investigators did not use did not use the STAR*D protocol-stipulated HRSD (Hamilton Rating Scale for Depression), but instead used a non-blinded clinic-administrated assessment, known as the QIDS-C, the Quick Inventory of Depressive Symptomatology. They also included 99 patients who scored as remitted on the HRSD at the outset of the study as well as 125 who scored as remitted when initiating their next-level treatment. “This inflated their report of outcomes.”

Unfortunately, the STAR*D investigators’ assertion of a 67% cumulative remission rate had already become accepted clinical wisdom. The NIMH’s director at the time, Thomas Insel, and an editorial in the American Journal of Psychiatry both claimed STAR*D participants achieved a 70% remission rate. “Our reanalysis found that in step 1, STAR*D’s remission and extent of improvement rates were substantially less than those reported in other open-label antidepressant comparator trials and then grew worse in steps 2-4.” The remission rate in step 1 was 25.5%; by step 4, it was only 10.4%.

Robert Whitaker further reported that Pigott and others discovered only 3% of the participants who entered the trial remitted and stayed well in the trial to its end in one year. One of the STAR*D investigators thought Pigott’s analysis was “reasonable and not incompatible with what we had reported.” That was 13 years ago and as of yet, there hasn’t been a public acknowledgement that these protocol violations were a form of scientific misconduct.

Yet, there has been no public acknowledgement by the American Psychiatric Association (APA) of this scientific misconduct. There has been no call by the APA—or academic psychiatrists in the United States—to retract the studies that reported the inflated remission rates. There has been no censure of the STAR*D investigators for their scientific misconduct. Instead, they have, for the most part, retained their status as leaders in the field.

Thus, given the documented record of scientific misconduct, in the largest and most important trial of antidepressants ever conducted, there is only one conclusion to draw: In American psychiatry, scientific misconduct is an accepted practice.

Whitaker said this presented a challenge to American citizens. If the American Psychiatric Association would not police its own research, it was up to the public to demand the STAR*D paper be withdrawn from the American Journal of Psychiatry. “As STAR*D was designed to guide clinical care, it is of great public health importance that this be done.”

He persuasively argued that there had been an intent to deceive. He said once Pigott and colleagues identified the deviations from the STAR*D protocol (which they did initially in 2010), “the STAR*D investigators’ ‘intent to deceive’ was evident.” After Pigott made the protocol and other key documents available in 2011 on two blogs for the Mad in America website, the scientific community could see the deception.

Their recent RIAT publication [in August of 2023] makes it possible to put together a precise numerical accounting of how the STAR*D investigators’ research misconduct, which unfolded step by step as they published three articles in 2006, served to inflate the reported remission rate. This MIA Report lays out that chronology of deceit. Indeed, readers might think of this MIA Report as a presentation to a jury. Does the evidence show that the STAR*D’s summary finding of a 67% cumulative remission rate was a fabrication, with this research misconduct born from a desire to preserve societal belief in the effectiveness of antidepressants?

In Psychiatry Under the Influence Whitaker and his coauthor Lisa Cosgrove wrote about how the STAR*D trial was an example of institutional corruption. They said there were two forms of institutional corruption, or economies of influence, driving that corruption: psychiatry’s guild interests and the extensive financial ties the STAR*D investigators had with the pharmaceutical industry. They said:

Although this was a NIMH-funded trial, industry influence was indirectly present during the trial. Rush and at least seven other STAR*D investigators had financial ties to Forest Laboratories, the manufacturer of Celexa. The investigators’ collective disclosure statement revealed hundreds of ties to pharmaceutical companies, with many investigators reporting that they had served as both consultants and speakers. Yet, given that this was a NIMH-funded trial, STAR*D couldn’t be blamed on the drug companies, and it could be argued that the “corruption” seen here far outstripped anything seen in a commercial trial of the SSRI antidepressants. (p. 129)

Whitaker said the American Psychiatric Association is best understood as a trade association that promotes the financial and professional interests of its members. The APA has long touted antidepressants as effective and safe treatment. He thought if the STAR*D results has been accurately reported, they would have derailed society’s belief in the safety and efficacy of antidepressants. The STAR*D investigators were, in a business sense, protecting one of their primary “products.” And they were safeguarding the public image of their profession.

This research misconduct has done extraordinary harm to the American public, and, it can be argued, to the global public. As this was the study designed to assess outcomes in real-world patients and guide future clinical care, if the outcomes had been honestly reported, consistent with accepted scientific standards, the public would have had reason to question the effectiveness of antidepressants and thus, at the very least, been cautious about their use. But the fraud created a soundbite—a 67% remission rate in real-world patients—that provided reason for the public to believe in their effectiveness, and a soundbite for media to trot out when new questions were raised about this class of drugs.

This, of course, is fraud that violates informed consent principles in medicine. The NIMH and the STAR*D investigators, with their promotion of a false remission rate, were committing an act that, if a doctor knowingly misled his or her patient in this way, would constitute medical battery.

This cataloging of harm done extends to those who prescribe antidepressants. Primary care physicians, psychiatrists, and others in the mental health field who want to do right by their patients have been misled about their effectiveness in real-world patients by this fraud.

The harm also extends to psychiatry’s reputation with the public. The STAR*D scandal, as it becomes known, fuels the public criticism of psychiatry that the field so resents.

Believing this to be a matter of great importance to public health, Mad in America put up a petition on change.org urging the American Journal of Psychiatry to retract the November 2006 article on the STAR*D results. Their hope is that the petition will circulate widely on social media and produce a public call for retraction that will grow too loud for the American Journal of Psychiatry to ignore. Whitaker hoped the publication of the August 2023 article by Pigott and others linked above in the prestigious journal British Medical Journal will lead the American Journal of Psychiatry to retract a paper that told a fabricated story about the outcome of the STAR*D study.

On December 1, 2023 the American Journal of Psychiatry published a letter from John Rush and four other STAR*D researchers, “The STAR*D Data Remain Strong: Reply to Pigott et al.” The researchers claimed the analytic approach by Pigott et al. had significant methodological flaws and stood by their results and methodology in STAR*D. They further said the effectiveness trials of their study were designed “to be more inclusive and representative of the real world than efficacy trials.” Pigott et al failed to recognize this rationale for the inclusion of the 941 patients in the original analyses that were eliminated from their reanalyses by Pigott et al.

The rationale for removing these participants from the longitudinal analysis appears to reflect a studious misunderstanding of the aims of the Rush et al. paper, with the resulting large difference in remission rates most likely the result of exclusion by Pigott et al. of hundreds of patients with low symptoms scores at the time of study exit.

Robert Whitaker responded to the letter in “After MIA Calls for Retraction of STAR*D Article, Study Authors Double Down.” He said the STAR*D investigators had inflated the “cumulative remission rate” in four principal ways. First by including ineligible patients in their tally of remitted patients. Second, by switching outcome measures. Third, by categorizing early dropouts as non-evaluable patients. Fourth, by calculating a “theoretical” remission rate.

By the end of their letter, they again affirmed the 67% cumulative remission rate. Whitaker thought they had “doubled-down on the fraud they committed in their 2006 summary report of STAR*D outcomes.”

Now that the STAR*D authors have “defended” their work, all the public really needs to know is this: The STAR*D investigators, by including 931 patients who weren’t eligible for the study in their final tally of cumulative remissions, greatly inflated that bottom-line outcome. That is research fraud, and in their letter to the editor, rather than admit that these patients weren’t eligible for the study, they instead falsely accused Pigott and colleagues of “creating” their own “post-hoc” criteria to remove those with “large improvements” in symptom scores from their re-analysis.

Whitaker said the STAR*D scandal evolved into a litmus test for psychiatry. Would they acknowledge the research misconduct and inform the public of how the STAR*S study had been compromised? Was it okay to deceive the public in this way? “And now, with this letter to the editor, we know the answer to that litmus test.”

01/9/24

Dimming the Experience of Pleasure and Addiction

pexels.com

Neuroscience News reported on a recent study led by researchers from the National Institute on Drug Abuse (NIDA) and other federal agencies that found the brain’s ‘salience network’ was only activated when drugs were taken intravenously or smoked, but not ingested orally. “When drugs enter the brain quickly, such as through injection or smoking, they are more addictive than when they enter the brain more slowly, such as when they are taken orally.” The study suggests there’s new information on what may be behind the difference.

Nora Volkow, senior author of the study said, “We’ve known for a long time that the faster a drug enters the brain, the more addictive it is – but we haven’t known exactly why.” Using new imaging technology, the researchers believe they may now have an understanding of why this is. “Understanding the brain mechanisms that underlie addiction is crucial for informing prevention interventions, developing new therapies for substance use disorders, and addressing the overdose crisis.”

The researchers conducted a double-blind, randomized, counterbalanced clinical trial that used simultaneous PET/fMRI imaging. There were twenty adults who participated in the trial. Over three separate sessions, they received either a small dose of placebo or methylphenidate (Ritalin), orally or intravenously. After the participants received the study drug or placebo, the researchers looked at the differences in dopamine levels (through PET imaging) and brain activity (through fMRI imaging). The participants also reported their subjective experience of euphoria in response to the drug.

Consistent with previous research, the PET scan showed when participants received the methylphenidate orally, their dopamine rate peaked more than an hour after administration. However, participants who received methylphenidate intravenously, peaked within 5 to 10 minutes of administration. The fMRI of the participants indicated the ventromedial prefrontal cortex (where we process risk and fear) was less active after both oral and intravenous drug use. “However, two brain regions, the dorsal anterior cingulate cortex [associated with learning and self-control] and the insula [linked with salience detection and addiction], which are part of the brain’s salience network, were activated only after receiving the injection of methylphenidate, the more addictive route of drug administration.” The same areas of the brain were not activated after taking methylphenidate orally.

The salience network of the brain attributes value to things in our environment. It is important for recognizing and translating internal bodily sensations, like the euphoric effects of drugs. “This research adds to a growing body of evidence documenting the important role that the salience network appears to play in substance use and addiction.” Interestingly, other studies have shown when people experience damage to their insula (part of the brain’s salience network), they may have a complete remission of their addiction.

After receiving the drug intravenously, researchers noticed that the activity and connectivity of the salience network, observed via fMRI imaging, very closely paralleled almost every participant’s subjective experience of feeling high. When the imaging showed increased activity in this part of the brain, participants’ reports of feeling high increased.

When the imaging showed decreasing activity in the salience network, participants’ reports of feeling high decreased. Researchers theorize that the network identified in this study is relevant not just for the chemical action of the drug, but also the conscious experience of drug reward.

The authors indicated a next step would be to see whether inhibiting the salience network when someone takes a drug effectively blocks the feeling of being high. This would further support the salience network as a target for the treatment of substance use disorders. The lead author of the study said, “I’ve been doing imaging research for over a decade now, and I have never seen such consistent and clear fMRI results across all participants in one of our studies.”

Manza et al, the study reported in Neuroscience and discussed above, said: “Together, these findings provide insight into how the salience network is critically linked to the pathophysiology of substance use disorder.” Among the considerations to note in the study, participants were naïve to stimulant drugs. The participants were also administered methylphenidate in a laboratory environment, which tends to inhibit the results. For example, other studies have shown adult males will drink significantly more alcohol when they are exposed to a simulated bar environment relative to a neutral laboratory setting. Manza et al further said:

Notably, our study identified two distinct circuits similar to the pattern of brain lesions leading to clinical remission of addiction. Patients who suffered stroke lesions to brain regions that had positive functional connectivity with dACC [dorsal anterior cinugulate] and insula (where we observed activation with fast dopamine increases), and lesions to brain regions that had negative functional connectivity with ventromedial prefrontal cortex (where we observed deactivation both with slow and fast dopamine increases) led to remission. Therefore, both studies support interventions to inhibit the dACC and insula and interventions to stimulate the ventromedial prefrontal cortex as strategies for the treatment of substance use disorder. Indeed, the dACC is being tested as a neuromodulation target to combat compulsive drug use with preliminary findings showing decreases in cocaine self-administration, cue-induced alcohol craving, and heavy drinking days. Critically, in the latter study, successful stimulation effects were associated with decreased connectivity between dACC and caudate. A key next step is to evaluate if inhibition of this circuit during drug administration blocks the subjective experience of drug reward, which could open new avenues to treat substance use disorders.

The Reward Pathway and Addiction

The significance of the above-described study demonstrating the importance of fast or slow dopamine increases in the develop of a substance use disorder can be understood by reviewing Carleton Erickson’s description of the Reward Pathway of the brain in his book, The Science of Addiction. Erickson capitalizes the word “Addiction” to represent when addiction progresses to the stage of physical dependence.

Drugs produce “Addiction” in the mesolimbic dopamine system (MDS), the pleasure pathway located in the middle of the brain. It is believed that addiction problems develop when the function of these MDS neurotransmitter systems are disrupted due to genetic problems, long-term exposure to a drug, or a combination of these with environmental influences. The MDS generates signals in the part of the brain known as the ventral tegmental area (VTA), which releases dopamine (DA) into the nucleus accumbens (NAc). This release of DA into the NAc causes the feelings of pleasure, but not only from drugs. Other areas of the brain, like the basal ganglia, create a lasting record or memory that associates the good feelings with the from the drug use with the circumstances and environment in which they occur. See the figure below.

Release of DA in the NAc produces the sensation of pleasure. The anticipation of obtaining the drugs activates the limbic pathways in a way that leads to chemical dependence, to Addiction. This is why the above discussed study is significant and as the researchers speculated, opens “new avenues to treat substance use disorders.” But there is a potential problem with inhibiting connectivity between the dACC and insula in the treatment of substance use disorder as suggested.

In Never Enough, the neuroscientist Judith Grisel explained when activity in the mesolimbic pathway is prevented, the person is unable to experience pleasure. If activity in the mesolimbic pathway was prevented before a person used drugs, she said they’d “think the drugs were a complete waste of money.”

This might look like a cure, but … it is ethically problematic. Such an intervention would prevent pleasure from all sources, including things like food and sex. Most of the world has prohibited this sort of surgical intervention, although some nations, including China and the Soviet Union, are reportedly reducing relapse rates by employing this strategy. However, it doesn’t work all that well for seasoned addicts who use mainly to avoid unpleasant symptoms associated with withdrawal rather than seeking a high.

Addicts who are clearly suffering from their addiction are generally not willing to voluntarily undergo a procedure that would produce this form of anhedonia, a global deficit in their experience of pleasure. Most would rather go to prison or suffer other severe consequences, because then they could still experience transient pleasures. “Without dopamine in the nucleus accumbens, nothing, a letter from a friend, an especially beautiful sunset or piece of music, or even chocolate, would alleviate a persistently bleak existence.”

The research of Manza et al, reported by Neuroscience and discussed above is interesting. And when it’s replicated, it will become even more important to our growing knowledge of addiction. I would hope as we pursue the association of dopamine and addiction, that future research won’t dim the person’s experience of pleasure as it tries to cure their addiction.