02/1/22

Carrot-and-Stick Tactics of Purdue and the Sacklers

In the aftermath of frustration with the bankruptcy settlement with Purdue Pharma that shielded the Sackler family from any future legal action, the Metropolitan Museum of Art and the Sackler family announced the Sackler name would be removed from seven exhibit spaces. The New York Times said this was a significant break between the world’s largest museum and one of the world’s biggest benefactors. The Sackler family said they thought it was in the best interest of the museum and the mission it serves. “The museum had already severed ties to the family’s funding, announcing in 2019 that it would no longer accept gifts from the Sacklers, given their links to the maker of OxyContin.” Then a week later, a federal judge overturned the settlement that legally shielded members of the Sackler family from future litigation.

Reuters reported that U.S. District Judge Colleen McMahon said the New York bankruptcy court did not have the authority to grant the Sacklers legal protection from future opioid litigation. Attorney General Merrick Garland agreed, and was pleased by the ruling. He said: “The bankruptcy court did not have the authority to deprive victims of the opioid crisis of their right to sue the Sackler family.”

McMahon raised questions about more than $10 billion that Purdue distributed to the members of the Sackler family over a ten-year period of time preceding the company’s filing for bankruptcy. A statement from the family about the transfer of funds said, “Members of the Sackler family who served on Purdue’s board of directors acted ethically and lawfully, and the upcoming release of company documents will prove that fact in detail.”

The bankruptcy settlement was said to be worth $8 billion, a record payout by a pharmaceutical company. However, the Sackler family threatened to walk away and scuttle the settlement unless the legal protections were included. The family was to contribute over $4 billion of their personal funds to charitable assets over nine years as part of the settlement.

The Hill reported that in September 2021, U.S. Bankruptcy Judge Robert Drain approved the initial settlement plan. It would have led to the dissolution of Purdue Pharma and the transfer of its assets to a nonprofit company whose mission would be to fight the opioid crisis.

Representative Carolyn Maloney (D-N.Y.), Chair of the Committee on Oversight and Reform, said: “Today’s ruling striking down Purdue Pharma’s bankruptcy plan and its illegal releases for the Sacklers is a monumental step toward justice for the victims of the Sacklers’ cruel, deliberate plan to flood our communities with the highly addictive opioid, OxyContin.” She added,

The Sacklers must not be permitted to evade accountability by abusing our bankruptcy system, and I applaud the District Court for recognizing what I’ve long believed — that nonconsensual third-party releases are not only immoral and unjust, but also illegal.

Of course, Purdue will appeal the district court’s decision. Steve Miller, Purdue’s chairman, said:

While the district court decision does not affect Purdue’s rock-solid operational stability or its ability to produce its many medications safely and effectively, it will delay, and perhaps end, the ability of creditors, communities, and individuals to receive billions in value to abate the opioid crisis.

This sounds suspiciously like Purdue and the Sacklers are using a “carrot-and-stick” approach to their negotiations—the billions in settlement money as the carrot and the threat of rejecting the settlement without legal protection of the Sacklers from future opioid litigation as the stick.

Paul Pelletier, a former Department of Justice fraud chief and Beth Macy, a journalist and the author of Dopesick, wrote an opinion piece for STAT News. They noted that in late 2020, Purdue pled guilty to defrauding federal health agencies and violating anti-kickback laws. Although the Department of Justice won a $225 million civil settlement, it won’t collect on the $8.3 billion fine, as the company was already in bankruptcy. It failed to bring charges against any individuals for their roles in the company’s crimes. But the 2020 settlement did not close the door on criminal prosecution of Sackler family members.

Sacklers Avoiding Justice?

Fifteen years ago, prosecutors in western Virginia uncovered evidence of fraud and recommended multiple felony charges against the three top executives at Purdue. These charges included money laundering, conspiracy, misbranding, interstate wire and mail fraud. Pelletier and Macy said “the evidence of callous greed was chilling.” But political appointees at the DOJ, swayed by Purdue’s lawyers, refused to approve felony charges for the executives.

Purdue received a $600 million fine and pleaded guilty to “misbranding” OxyContin while marketing. The three executives pleaded to a misdemeanor “misbranding” charge, but did not admit any wrongdoing. The case was settled through a plea bargain and the evidence within the case forgotten until a copy of the Justice Department memo was leaked. For more information on this, see “Giving an Opioid Devil Its Due.”

The company had fired employees who tried to blow the whistle on its crimes and maneuvered to have reporters who were onto the story fired or removed from their beats. Sales reps were encouraged to allow doctors to believe — falsely — that morphine was stronger than OxyContin when executives knew the opposite was true. The company’s medical director, Dr. Paul Goldenheim, lied to Congress when he testified that executives hadn’t known until 2000 that OxyContin was being widely abused: in fact, they’d become aware of addiction-related abuse shortly after the drug’s introduction in 1996.

“A trial would have exposed the company’s OxyContin profits to forfeiture or prompted one of the executives to expose the magnitude of OxyContin scion Richard Sackler’s participation in the admitted crimes.”

Pelletier and Macy said after avoiding a legal trial related to the above investigation, they know the Sacklers and Purdue intensified their marketing of OxyContin. Purdue hired consultants to advise them how to “turbocharge” sales. They concentrated on well-known pill mills, and pushed the highest-dose pills. They also joined with other opioid makers to get around FDA regulators.

Beth Macy’s book, Dopesick was made into a television series. The show’s creator said it was “the trial that Purdue Pharma and the Sackler family never had.” As Pelletier and Macy pointed out, America is not supposed to rely on books and a movie for justice. “We pay taxes and give the Department of justice legal authority to enforce the law.” They said that Judge McMahon’s ruling was a win for accountability, “but it may not endure.”

So far, no criminal charges have been filed against any member of the Sackler family. But a new U.S. attorney for the federal district responsible for investigating the Sacklers has been sworn in. And Pelletier and Macy think he could be the perfect Special Prosecutor. We’ll have to wait and see if this makes a difference. Meanwhile, the Metropolitan Museum of Art continues to distance itself from the Sacklers and Purdue.

While the billionaire Sacklers may spend this holiday season ruminating on the ignominy of having their name removed from New York’s Metropolitan Museum of Art and other museums they showered with blood money, a million families across America will have to endure it without their children, spouses, parents, and friends whose lives were either eviscerated or cut short by opioids. It is shameful that, at least for now, they must live without justice, too.

For more information on the initial settlement, see: “It Doesn’t Seem Right.”

01/11/22

The Cost of Buprenorphine-Assisted Recovery

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As I was leaving a rescue mission in Pittsburgh, I saw a homeless man curled up in a fetal position in front of the building. He was unresponsive when I called out to him, so I went back inside and told someone to call 911. While I was doing this, another staff member got Narcan and administered it to the man. When the paramedics arrived, they were eventually able to convince him to go to the emergency department of a local hospital. But he refused further treatment services there and was released.

This is a typical response of those who experience a nonfatal opioid overdose. According to Davis et al in an article published in the Annals of Emergency Medicine, opioid users resist treatment with buprenorphine even though it significantly reduces overdose mortality. In an attempt to minimize this treatment void, some EMS paramedic units are administering buprenorphine to patients almost immediately after reviving them from an opioid overdose. STAT reported back in June of 2019 that New Jersey’s health commissioner authorized paramedics to offer the drug to patients after their overdose has been reversed with naloxone.

The first-in-the-nation model has a twofold purpose, health officials said: Beyond treating the withdrawal symptoms that can result from a naloxone revival, administering buprenorphine on scene could serve as an immediate transition to longer-term treatment.

Dr. Dan Ciccarone, a professor who studies heroin use and the opioid epidemic, said while the prehospital use of buprenorphine comes out of left field, “It’s a potentially brilliant idea.” He sees this as an attempt to treat the person in as well-meaning and patient-centric way as possible. “And that means naloxone plus a softer landing with buprenorphine.” Doctors in numerous emergency departments already prescribe buprenorphine in an effort to provide relief after reversing an overdose. Extending that ability to paramedics “is a new frontier.”

As a safeguard, New Jersey’s 1,900 paramedics will need to obtain permission from the emergency physician overseeing their unit before administering buprenorphine when responding to an overdose call. The supervising physician must have a DEA waiver [and undergo training] to prescribe buprenorphine, a spokeswoman said.

We need to think beyond how we’ve traditionally treated nonfatal opioid overdoses. A CDC press release indicated in the 12-months ending in April 2021, the estimated overdose deaths from opioids increased from 56,064 in April of 2020 to 75,673. Overall drug overdoses increased 28.5% during the same period of time. An interactive web dashboard is available and can gives you predicted overdose data for individual states. The overall increase in overdoses for the United States is 28.5%.

Pennsylvania was among the states hardest hit by the opioid epidemic. In 2018, it had one of the highest death rates from drug over doses, with 65% of 2,866 fatalities involving opioids. Policy responses made to mitigate the spread of COVID-19 in Pennsylvania made the problem worse. Analysis of data from the Pennsylvania Overdose Information Network for both fatal and nonfatal overdoses revealed statistically significant increases across some of the populations most affected by opioids before the pandemic.

In “Assessing the Relationships Between COVID-19 Stay-at-Home Orders and Opioid Overdoses,” the authors said the stay-at-home order in Pennsylvania contributed to a statistically significant increase in opioid overdoses compared with preceding months. See “Unintended Consequences of COVID-19” for more on this topic. It seems this increase in opioid overdoses may have partly motivated Pittsburgh to become only the third city in the country to announce a pilot group of Emergency Medical Services (EMS) paramedics that will administer prehospital buprenorphine.

On November 22, 2021, The Office of Community Health and Safety in Pittsburgh announced paramedics had completed training to administer prehospital buprenorphine and began implementing the practice over the weekend before Thanksgiving. In September, the Pennsylvania Department of Health Bureau of EMS approved the Prehospital Buprenorphine Pilot Program for the City of Pittsburgh’s EMS. The pilot program was designed by the Bureau of EMS in partnership with the Office of Community Health and Safety.

As part of the pilot, Advanced Life Support EMS units will be able to administer buprenorphine to patients experiencing opioid withdrawal regardless if that patient decides to go to the hospital. Patients will then be able to schedule a virtual follow up with the UPMC Medical Toxicology Bridge Clinic to have a consultation with a doctor within 24 hours to get a buprenorphine prescription and be connected to other critical harm reduction resources.

Advanced Life Support EMS units will be able to administer buprenorphine to patients experiencing opioid withdrawal regardless of whether they decide to go to the hospital. Patients will then be able to schedule a virtual follow up to have a consultation with a doctor within 24 hours in order to get a buprenorphine prescription and be connected to other harm reduction resources.

The mayor of Pittsburgh, Bill Peduto, said: “The opioid epidemic has deeply affected so many cities and communities. If tools like buprenorphine exist, we need to have them in our communities and with our emergency medical personnel.” The Pittsburgh Post-Gazette reported there has been a 58% increase in overdose-related calls between October of 2020 and July of 2021—the latest month the city had data on. See the following chart showing the drug overdose calls to EMS in Pittsburgh.

Research shows that buprenorphine-assisted recovery from opioid use decreases the likelihood of recurrent overdoses and death from overdoses while increasing the likelihood of the person engaging in recovery. Dr. Jody Glance said buprenorphine helps patients more comfortably stop using opioids by alleviating their withdrawal symptoms. “Once the person is stabilized on the medication, they will not have the same level of cravings or desire to use illicit opioids.” This stabilization allows the person to engage in activities to support their ongoing recovery.

Dr Glance said some people remain on buprenorphine because they believe it is saving their life. “A lot of people find that the medication is so helpful, that coming off of it is more risky than staying on it.” She added that sometimes people stay on buprenorphine for a long time. Like other chronic, relapsing illnesses, “with opioid use, a lot of times people need a medication on a more long-term basis.” For patients who want hospital treatment, the program allows them to schedule a follow up visit with The UPMC Medical Toxicology Outpatient Clinic to continue taking the drug.

While it is an amazing, almost miraculous tool, bringing relative stability to the lives of opioid addicts, it comes with a price. Buprenorphine is itself an opioid. The DEA classifies it as a Schedule III controlled substance. It’s effectiveness in alleviating withdrawal and minimizing cravings for licit and illicit opioids is based on this pharmacological fact. And long-term use of buprenorphine perpetuates some of the same neurochemical actions found in opioid use disorder.

In her book, Never Enough, Judith Grisel introduced what she said were the three laws of psychopharmacology. They are: 1) all drugs act by changing the rate of what is already going on in the brain; 2) all drugs have side effects; and 3) the brain of someone who misuses drugs adjusts by producing fewer neurotransmitters in the reward circuit, or by reducing the number of receptors that can receive signals. The psychopharmacological action of buprenorphine-assisted recovery on the brain continues to activate these principles.

Not only do we need to bring stability to the lives of addicts after a nonfatal overdose, we need to educate them about the potential consequences they face with long-term use of buprenorphine. Inform them of the cost they’ll pay for a buprenorphine-assisted recovery.

For more information on Judith Grisel and the significance of the three laws of psychopharmacology to addiction recovery, see “Never Enough and No Free Lunch” and “Never Enough and Adaptation.”

12/21/21

The Risks of Legalizing Marijuana in PA

Attempts to legalize recreational marijuana in PA with Senate Bill 350, the “Adult-Use Cannabis Act,” failed. But efforts to do so have not stopped. In September of 2021, State Representatives Jake Wheatley and Dan Frankel sponsored H.B. 2050, which would legalize adult-use recreational marijuana. Not to be outdone, State Senators Dan Laughlin and Sharif Street introduced Senate Bill 473 to legalize recreational marijuana in October of 2021. Laughlin and Street believe their bi-partisan bill has the best chance of ultimately legalizing recreational marijuana in Pennsylvania, and could generate between $400 million and $1 billion of new tax revenue. But what are the risks of such legislative action?

Larry Weigand, who was running for sheriff in Delaware County, said he understood that social views on marijuana use have changed and polls report most Pennsylvanians support legalization. “But the social views of intoxication and driving under the influence have not; to the contrary, they have become more stringent.” He thought the legislature needs to be considerate of both sides of the issues, considering all who would be affected, “including the non-users of marijuana and law enforcement.”

Negative Consequences in Colorado

Consider the negative consequences of legalization in Colorado reported in The New York Times, “Reefer Madness or Pot Paradise?” Legalization coincided with a 20 percent rise in violent crime rates in Colorado, while marijuana-related arrests fell by half. Although low-level marijuana charges dropped, racial discrepancies in drug arrests persisted. African-Americans were still being arrested on marijuana charges almost twice as often. One of the state legislators who endorsed the Colorado ballot measure that legalized recreational marijuana said: “You don’t see drug-addled people roaming the streets, but we haven’t created a utopia.”

Since recreational sales began in 2014, more people in Colorado are going to emergency rooms for marijuana-related problems. Hospitals report higher rates of mental health cases associated with marijuana. An emergency room physician and researcher with the University of Colorado Hospital, Andrew Monte, analyzed hospital data that showed more people were arriving at ERs for marijuana-related reasons. He said, “There’s a disconnect between what was proposed as a completely safe drug.”

Other researchers in “Marijuana and acute health care contacts in Colorado” reported that marijuana-related ER patients were five times as likely to have a mental-health issue as those with other cases. “As more states legalize marijuana, it is important to address public education and youth prevention, and understand the impact on mental health disorders.” The most frequent primary diagnosis of ER visits with marijuana-related billing codes compared to those without marijuana-related billing codes was for mental illness.

Among primary diagnosis categories, mental illness was more prevalent in ED visits and hospitalizations with marijuana-related billing codes. Examination of the role marijuana plays in mental health driven healthcare encounters is critical given the relationship between drug use disorders and mental health disorders. While it is unclear whether this finding is reflective of changes due to a legal market, it clearly prioritizes the consequences of marijuana use within a mental health population as a priority area for further research.

Psychosis and Marijuana

While political rhetoric in favor of legalization is calling for the end of marijuana “prohibition,” scientific research is forming a consensus that THC, the psychoactive cannabinoid in marijuana, induces psychotic symptoms. A research article published in The Lancet Psychiatry, “Psychiatric symptoms caused by cannabis constituents,” included additional evidence for that consensus. The authors readily acknowledged that cannabis was one of the most widely used psychoactive substances worldwide, with 6-7% of Europeans and 15.3% of Americans using it each year. Decriminalization and legalization trends were happening globally, with Canada, Uruguay and a growing number of US state permitting the sale and recreational use of marijuana. However,

Given the projected increase in rates of cannabis use, the increasing potency of cannabis and cannabis-based products, and the burgeoning interest in the therapeutic potential of cannabinoids, it is timely to assess the psychiatric effects of cannabis constituents.

The researchers demonstrated that THC induced significant increases of symptoms as they were reported on psychiatric scales, the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS). Positive symptoms included delusions and hallucinations; negative symptoms included blunted affect and amotivation; and general symptoms included depression and anxiety. Effect sizes were greater for positive symptoms than negative symptoms, but not for general symptoms. This finding suggested that THC induced positive symptoms like psychosis to a greater extent than negative symptoms.

Speaking with Healio Psychiatry in “THC linked to psychiatric symptoms with large effect sizes,” Oliver Howes, one of the co-authors, said: “These findings highlight a potential risk of taking THC-containing cannabis products, and, importantly, show that THC can lead to short-term psychotic symptoms even in people with no history of mental illness or other risk factors.” While there has been previous evidence for the association of positive psychiatric symptoms and marijuana, Howes said he was surprised that THC induced other psychiatric symptoms like social withdrawal.

In conclusion, these findings demonstrate that the acute administration of THC induces positive, negative, and general psychiatric symptoms with large effect sizes. By contrast, CBD does not induce psychiatric symptoms, and there is inconclusive evidence that it moderates the induction of psychiatric symptoms by THC. These effects are larger with intravenous administration than with inhaled administration, and tobacco smokers have less severe positive symptoms. These findings highlight the acute risks of cannabis use, which are highly relevant as medical, societal, and political interest in cannabinoids continues to grow.

In a related editorial published in the same issue of The Lancet Psychiatry, “THC: harmful even in low doses?”, Carsten Hjorthøj, and Christine Merrild Posselt said there was a growing scientific consensus that marijuana does have a causal role in the development of psychosis. And they thought the association seems to be bidirectional. “In some people, cannabis leads to incident psychosis, whereas in other people, psychosis leads to incident cannabis use.” However, they noted this consensus was not reflected in mainstream public discourses, “which have a major effect on the political agenda to decriminalize cannabis.”

Referring to “Psychiatric symptoms caused by cannabis constituents,” Hjorthøj and Posselt said finding large effect sizes for general psychiatric symptoms, even with low doses of THC, was “extremely important and worrying.”

Moreover, the authors failed to find any clear evidence that concurrent administration of cannabidiol (CBD) reduced these symptoms. Indeed, such an ameliorating effect was observed in only one of four included studies. This finding is notable because CBD in particular is being touted as a potential wonder drug with antipsychotic, anxiolytic, and other properties. . . As Hindley and colleagues have clearly demonstrated, there are at least transient psychiatric symptoms associated with even relatively low doses of THC. Of course, this result should not be extrapolated as meaning that single doses of THC will eventually lead to schizophrenia or other severe disorders. However, it might be prudent to extrapolate and paraphrase the words of Moore and colleagues from their 2007 meta-analysis to apply to both recreational and medicinal use of THC-containing cannabis: “there is sufficient evidence to warn people that using THC could increase their risk of developing psychiatric symptoms or even a psychotic illness”.

So, pointing to the potential for increased tax revenue, the opportunity for new jobs in the marijuana industry, and all the other supposed benefits of ending the so-called ‘prohibition’ of recreational marijuana is not enough. Pennsylvania also needs to consider the risks to its citizens if it legalizes recreational marijuana. And one of them is people who use cannabis increase their risk of experiencing psychosis and other psychiatric symptoms.

There are several other articles on the risk of psychosis with marijuana on this website, and the concerns for Pennsylvania if recreational marijuana is legalized in the Commonwealth. Here are a few: “Cannabis and Psychosis: More Reality Than Satire,” “Telling the Truth About Marijuana and Psychosis,” “The Business of Legalizing Marijuana in PA,” and “Should Pennsylvania Go ‘Full Colorado’ with Marijuana?” Part 1 and Part 2.

11/30/21

Not as a Stand-Alone Therapy

The pharmaceutical company Alkermes began planning an alcohol dependency awareness campaign before the pandemic, but its launch in May of 2021 coincidently happened to overlap with the publicity of increasing of alcohol use and misuse during the pandemic. Fierce Pharma noted that while all drinking is not problematic, spikes in binge drinking particularly among women, are causes for concern. The Alkermes campaign emphasizes that alcohol dependence is a disease, not a moral failing. The VP and general manager of addiction marketing at Alkermes said, the disease model was useful for people to see problem drinking as a medical condition, “that there are medical criteria that you can assess and look at your own situation and make informed choices.”

The campaign initially centered on a new website that asks on the front page, “Is it time to rethink your relationship with alcohol?” There are personal stories of people’s “journey with alcohol dependence and recovery.” There is a link to a questionnaire developed by the National Institutes of Health (NIH) that was based on the criteria for alcohol dependence outlined in the DSM-IV. Finally, there is a link to “Learn more about a treatment option,” which leads you to a separate website for Alkermes’ addiction drug, Vivitrol. But there is more going on here than just following a breadcrumb trail from a public service campaign to a treatment option for alcohol dependence.

If you follow the link to the Vivitrol website, you are asked if you are ready for the next step in your recovery. What follows is largely a repeat of information that is contained in the medication guide for Vivitrol. Even though this Alkermes ad campaign is aimed to treat alcohol dependence, there is a significant amount of time spent there describing and discussing the risk of opioid overdose and sudden opioid withdrawal. What you won’t find on the website is information on exactly how Vivitrol treats alcohol dependence! Why would a marketing campaign for an alcohol dependence treatment spend so much effort cautioning against how Vivitrol could create safety issues with opioids?

Because Alkermes has been known to gloss over safety risks in its promotion of Vivitrol to treat opioid addiction. Not only is Vivitrol used to treat alcohol dependence, it is also approved as a medication-assisted treatment for opioid use disorder.

The FDA previously cited Alkermes in a warning letter for omitting safety risks in an ad for Vivitrol. “In the letter, the agency said it had contacted the company twice before issuing the warning.” The FDA was concerned enough with Alkermes’ apparent disregard of it previous letters that it also issued a press release that announced this action. The press release said Alkermes had omitted warnings about the most serious risks associated with the drug from promotional materials.

While the print advertisement contains claims and representations about the drug’s benefits, it fails to adequately communicate important warnings and precautions listed in the product labeling, including vulnerability to opioid overdose, a potentially fatal risk.

What you won’t find on the new Vivitrol website or in the Vivitrol medication guide is information on exactly how it treats alcohol dependence and what are the specific concerns in using Vivitrol to treat alcohol dependence. The active ingredient in Vivitrol is naltrexone, which has been used to treat alcohol use disorder for over twenty years. It works by suppressing cravings for alcohol and opioid drugs. It does this by binding to opioid receptors in the person’s brain, which also removes any opioid drugs binding with these receptors and can precipitate sudden opioid withdrawal. The medication guide for Vivitrol cautions that anyone receiving the drug should be opioid-free for at least 7 to 14 days before receiving Vivitrol, since the injection “may cause you to suddenly have symptoms of opioid withdrawal.”

The American Addiction Centers website said the following about naltrexone and naltrexone’s effectiveness:

Individuals with moderate to severe alcohol use disorders [i.e., alcohol dependence] who are using naltrexone may experience withdrawal symptoms if they stop drinking that can be potentially fatal due to the development of seizures. These individuals should consult with an addiction medicine physician or psychiatrist before discontinuing their use of alcohol. Research findings are mixed, but overall, they tend to support the notion that individuals who use naltrexone to treat alcohol abuse reduce the total amount of alcohol they consume and observe a reduction in the number of times they drink alcohol. In addition, heavy drinkers often notice significant reductions in alcohol use. However, the research does not indicate that the use of naltrexone is effective at assisting individuals in remaining totally abstinent, but it does most likely result in a significant reduction in cravings for alcohol and an overall reduction in the amount of alcohol consumed.

Counterintuitively, naltrexone products like Vivitrol are not effective in helping someone abstain from alcohol. But as the American Addiction Centers website noted, it is used in the Sinclair Method to help the individual reduce their alcohol intake. This “treatment” method actually encourages individuals to drink, but only after taking naltrexone before they start drinking. Naltrexone blocks endorphins from being released when alcohol is consumed. Endorphins are naturally occurring opiates in the brain. “When the endorphins are blocked, there is no ‘buzz’ or rewarding experience, and the alcohol doesn’t make you feel the pleasure that drives you to drink excessively.”

The Sinclair Method sees alcoholism as primarily a learned behavior that can be extinguished by naltrexone systematically closing off this reward circuit in the brain. But naltrexone (as ReVia or Vivitrol) does not close the door on how alcohol effects functional impairments, such as a loss of motor coordination, decreased response time, slowed rate of thinking and judgement. ReVia is a tablet or capsule of naltrexone that you take about an hour before you plan to drink and can be skipped if you plan on drinking and want to feel the euphoria from drinking. With Vivitrol, you have some level of naltrexone in your system for up to a month, meaning that the blocking effect when drinking is stronger the closer you are to when you received your Vivitrol shot.

Vivitrol may be effective in reducing your overall alcohol intake when drinking, but it does not seem to be effective in helping you remain totally abstinent. Moreover, if your alcohol intake is substantial enough, and Vivitrol successfully helps you reduce your craving for alcohol and the amount of alcohol you consume too rapidly, using it can result in seizures and other alcohol withdrawal symptoms. If you use or abuse opioids along with drinking alcohol, Vivitrol can also throw you into sudden opioid withdrawal. It also decreases your tolerance level for opioids and makes you vulnerable to opioid overdose, if you use opioids.

Above, I noted where the Alkermes campaign for Vivitrol as a treatment for alcohol dependence emphasized it was a medical condition with criteria that could be assessed by an individual as they make an informed choice on whether Vivitrol was right for them. Alcohol dependence is never just a medical condition. And recovery is not simply learning to abstain or drastically curtail your alcohol use. It is also about making radical changes in your feeling, thinking and behavior around alcohol. To its credit, Alkermes did emphasize that for Vivitrol to be effective, it must be used with other alcohol or drug recovery programs. So, Vivitrol may work in some cases with alcohol abuse, but not as a stand-alone therapy for alcohol dependence.

Remember the final advice Alkermes gives: “Vivitrol may not work for everyone.”

11/9/21

The Unseen Surge of Alcohol Use

Although the increase in overdose deaths preceded the COVID pandemic, the pandemic seems to have accelerated the trend. In December of 2020, the CDC reported that drug overdose deaths in the U.S. rose 29.4% that year, mostly from illicitly manufactured fentanyl. Overdose deaths involving psychostimulants increased 10 times from 2009 to 2019. This increase was a mixture of opioids and psychostimulants as well as psychostimulants alone. But all the attention on these two drug classes seems to have overlooked the unseen surge of COVID-related increases with another drug—alcohol.

Using death certificate data from the National Center for Health Statistics, White et al found that almost 1 million people died from alcohol-related causes between 1999 and 2017. The number of death certificates mentioning alcohol more than doubled during that time frame. The Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), George Koob, said:

Alcohol is not a benign substance and there are many ways it can contribute to mortality. The current findings suggest that alcohol-related deaths involving injuries, overdoses, and chronic diseases are increasing across a wide swath of the population. The report is a wakeup call to the growing threat alcohol poses to public health.

The researchers found that nearly half of alcohol-related deaths were from liver disease (31%) or overdoses on alcohol alone or with other drugs (18%). By the end of the study, alcohol-related deaths were increasing among people in almost every age, racial and ethnic group. Death rates increased for women (85%) more than men (35%). Women also appeared to be at a greater risk for several alcohol-related consequences than men—including cardio-vascular disease, liver disease, alcohol use disorder. Dr. Koob said:

Taken together, the findings of this study and others suggests that alcohol-related harms are increasing at multiple levels – from ED visits and hospitalizations to deaths. We know that the contribution of alcohol often fails to make it onto death certificates. Better surveillance of alcohol involvement in mortality is essential in order to better understand and address the impact of alcohol on public health.

The researchers said alcohol-related deaths were highest among males, individuals between 45 and 74 years of age, and non-Hispanic American Indians or Alaska Natives. Rates increased for all age-groups except 16 to 20 and 75 and over. The largest increase was among non-Hispanic White females. These findings confirm the increasing burden of alcohol on public health.

On his blog, William White observed how the alarm over recent drug surges with opioids and methamphetamines could be obscuring surges in alcohol consumption and its related consequences. In addition to the White et al study, William White also referred to Sherk et al, whose researchers found that even light or moderate alcohol consumption increased the risk for a number of health consequences, including cancer, heart disease and traumatic injuries. More than one quarter (27%) of alcohol-related hospital stays were experienced by individuals who drank within the weekly guidelines.

The low-risk drinking guidelines for men were no more than 14 drinks per week and no more than 4 drinks per day. Low risk guidelines for women were no more than 7 drinks per week and no more than 3 drinks per day. Sherk et al concluded drinkers who followed weekly low-risk drinking guidelines were not immune from harm. They suggested guidelines of one drink per day for both sexes. The researchers clearly demonstrated that alcohol abuse and the related consequences were increasing before the COVID pandemic.

Alcohol Abuse and COVID

As stay-at-home orders began in some US states to lessen COVID-19 transmission in March of 2020, Nielsen reported a 54% increase in national sales of alcohol for the week ending Mach 21, 2020. The World Health Organization warned that alcohol use could potentially worsen health vulnerability, risk-taking behaviors, mental health issues and violence. The WHO suggested existing rules and regulations to protect health and reduce the harm caused by alcohol, such as restricting access, should be reinforced during the COVID-19 pandemic. “Any relaxation of regulations or their reinforcement should be avoided.”

Pollard, Tucker and Green looked at “Changes in Adult Alcohol Use and Consequences During the COVID-19 Pandemic in the US.” The data were collected using the RAND Corporation American Life Panel (ALP), a nationally representative, probability-sample panel of 6,000 participants. A sample of 2,615 ALP members ages, 30-to-80, were invited to participate in the baseline survey.

Comparisons before and during the COVID-19 pandemic were made on the number of days participants reported any alcohol use and heavy drinking, and the average number of drinks consumed over the previous 30 days. Heavy drinking was defined as 5 or more drinks for men and 4 or more drinks for women within a couple of hours. Adverse consequences were assessed by the 15-item Short Inventory of Problems associated with alcohol use in the previous 3 months. Comparisons were made overall, and across self-reported sex, age, and race/ethnicity.

These data provide evidence of changes in alcohol use and associated consequences during the COVID-19 pandemic. In addition to a range of negative physical health associations, excessive alcohol use may lead to or worsen existing mental health problems, such as anxiety or depression, which may themselves be increasing during COVID-19. The population level changes for women, younger, and non-Hispanic White individuals highlight that health systems may need to educate consumers through print or online media about increased alcohol use during the pandemic and identify factors associated with susceptibility and resilience to the impacts of COVID-19.

It does seem that concern with overdoses from opioids and methamphetamine in the midst of COVID overshadowed the growing problem with increasing alcohol consumption and its related consequences during the pandemic. William White observed that alcohol use is historically pervasive in the U.S. and “so infused into the cultural water in which we all swim that we fail to see it. That blindness has exacted, and continues to exact, an enormous toll on individuals, families, and communities.” The findings of the above discussed research studies reinforce the need for continued efforts with public and professional alcohol-related education, alcohol treatment resources, screening for alcohol problems and recovery support for individuals and families effected by alcohol use disorders. We cannot let concerns with the pandemic or opioid epidemic draw our attention away from the growing problem with alcohol-related deaths.

10/12/21

Unintended Consequences of COVID-19

On December 17, 2020, while the country’s attention was focused on the just-approved COVID vaccines, the CDC released a health advisory that noted substantial increases in drug overdose deaths across the U.S. Then, the report estimated that there were 81,230 drug overdose deaths in the 12-months ending in May 2020. This represented a worsening of the drug overdose epidemic in the U.S. and was the largest number of drug overdoses ever recorded for a 12-month time period. The CDC report said it appeared that drug overdose deaths accelerated during the COVID-19 pandemic. But then a new CDC report released in July of 2021 reported the number of overdose deaths had increased to 92,183 in December of 2020.

The July 2021 CDC report contains interactive figures showing the month-ending counts of overdose deaths by drug class and by states. From December of 2019 until December of 2020 California overdose deaths increased 45.9%; New York State, 37.3%; New York City, 36.6%. The states with the highest increases of overdose deaths were: Vermont, 57.6%; West Virginia, 55.6%; Kentucky, 53.7%; and South Carolina, 52.8%. The overall increase for the U.S. was 29.6%. See the July 2021 CDC report for more information.

A public health researcher for Brown University said to AP News this was a “staggering loss of human life.” While the nation was already struggling with a serious overdose epidemic, “COVID has greatly exacerbated the crisis.” Lockdowns and other restrictions during the pandemic made treatment harder to get. The increased deaths are most likely from people who were already struggling with addiction. Suspensions of evictions and extended unemployment benefits meant there was more money than usual to spend on drugs.

According to Shannon Monnat, a sociology professor at Syracuse University, what is really driving the surge in overdoses is an increasingly poisoned drug supply. “Nearly all of this increase is fentanyl contamination in some way. Heroin is contaminated. Cocaine is contaminated. Methamphetamine is contaminated.”

Reuters reported that during the pandemic, many drug programs were not able to operate. Restrictions meant therapy sessions were done by Zoom, which are not as impactful as in person face-to-face contact. Indirectly, pandemic lockdowns likely contributed to the increase in overdose deaths. The lockdowns intensified feelings of isolation, which is a factor in anxiety and depression, which leads to drug abuse. A health policy expert at John Hopkins Bloomberg School of Public Health estimated on a day-to-day basis, the U.S. is now seeing more overdose deaths than COVID-19 deaths.

In “Drug overdose deaths accelerating due to the pandemic,” the director of the CDC said the disruption of daily life from COVID-19 hit those with substance use disorder hard. “As we continue the fight to end this pandemic, it’s important to not lose sight of different groups being affected in other ways. We need to take care of people suffering from unintended consequences.” Again, we see the problems from fentanyl contamination. Opioids, primarily illegally manufactured fentanyl, were largely responsible for most of the overdose deaths. Synthetic opioid fatalities rose 38.4% from 2019 to 2020.

Recently, the American Medical Association noted a similar spike in overdose deaths driven by opioid deaths. The past president of the American Medical Association, Patrice Harris, warned of the necessity to continue to pay attention to health issues other than COVID. She said:

It is imperative that we continue to talk about other health issues that are impacting our nation . . . We are appropriately focused on COVID, it is still top of mind for most people, and it’s understandable that we can lose focus on other issues … but we still have to make sure we are focused on the overdose epidemic that we continue to experience in this country.

There was a study in in JAMA Network Open, “Trends in Drug Overdose Mortality in Ohio,” that looked at the overdose deaths in Ohio during the first seven months of the pandemic. Fatal overdoses rose sharply from the declaration of the pandemic on March 11^th 2020 to the week of May 31^st 2020, an increase of 70.6%. The initial spike in deaths was most pronounced for the youngest adults, those up to and including the age of 24. However, fatal overdoses followed a similar pattern in all age groups, including those 65 years and older. See the follow chart from the JAMA article.

Another study published in the Journal of Drug Issues assessed the relationships between COVID-19 stay-at-home orders and opioid overdoses in Pennsylvania. The authors said in an article for the Fix that Pennsylvania was one of the hardest hit states by the opioid epidemic. They found statistically significant increases in overdoses with heroin, fentanyl, fentanyl analogs or other synthetic opioids, pharmaceutical opioids and carfentanil. The researchers suggested in the Journal of Drug Issues that the observed increases were likely to be underestimates because of undercounts of monthly overdose incidents. They recommended these drug clsses be continuously monitored for changing patterns of use to help guide the most effective treatment interventions.

This analysis suggests that the onset of COVID-19 in the state of Pennsylvania, and resulting policy responses to mitigate infection, created unintended consequences for opioid overdose. These unforeseen outcomes obligate attention to how economic effects of the pandemic, coupled with mental health stress and other triggers for addiction, complicate and undermine patterns of opioid use and misuse, and emphasize the need for opioid use to be addressed alongside efforts to mitigate and manage COVID-19 infection.

It was pointed out how the economic recession associated with the pandemic undermined housing policy and access, “which will have lingering effects for social cohesion, access to medical care, and consistent routines critical for addiction management.” Percentages of fatal versus nonfatal overdoses remained relatively constant throughout the study at 16-17%. Heroin accounted for the largest percent (65%) of the total reported opioid-related overdose cases, followed by fentanyl (14%) and the unknown drug class (14%). “Increased mental health stress, social isolation, and economic uncertainty will likely continue to affect those most vulnerable to addiction and relapse.”

The double impact of COVID-19 and drug overdoses induced a drop in life expectancy for 2020. The CDC reported that life expectancy at birth for 2020 was 77.3 years, a decrease of 1.5 years from 78.8 in 2019. This was the lowest it has been since 2003. The decline in life expectancy was primarily due to COVID-19 (73.8% of the negative effect), unintentional injuries (11.2%), and homicide (3.1%). “Increases in unintentional injury deaths in 2020 were largely driven by drug overdose deaths.”

“The Leading Causes of Death in the US for 2020,” published in JAMA, found that COVID-19 was the third leading cause-of-death after heart disease and cancer. There were substantial increases from 2019 to 2020 for several leading causes. Heart disease deaths increased by 4.8%; unintentional injury by 11.1%; Alzheimer disease by 9.8%; and diabetes by 15.4%. Early estimates of life expectancy at birth for January 2020 to June 2020 showed declines not seen since World War II. See the following table taken from “The Leading Causes of Death in the US for 2020.”

The influence of the pandemic on the opioid epidemic has not gone unnoticed by the White House. In March of 2021, President Biden released a Statement of Drug Policy Priorities that said illicitly manufactured fentanyl and synthetic opioids other than methadone (SOOTM) have been the main influence behind the increase. However, overdose deaths from cocaine and other psychostimulants like methamphetamine have also risen. “New data suggest that COVID-19 has exacerbated the epidemic.” The American Rescue Plan, signed into law in March of 2021, set the following drug policy priorities for the administration:

Expanding access to evidence-based treatment;
Advancing racial equity issues in our approach to drug policy;
Enhancing evidence-based harm reduction efforts;
Supporting evidence-based prevention efforts to reduce youth substance use;
Reducing the supply of illicit substances; Advancing recovery-ready workplaces and expanding the addiction workforce; and
Expanding access to recovery support services.

Concern over the entwined consequences of the COVID-19 pandemic and the opioid epidemic exist beyond the US. In an opinion article for the BMJ, Ian Hamilton noted how the COVID-19 pandemic has amplified inequalities such as poverty, unemployment, poor housing and homelessness in the UK. He said these inequalities have been felt most acutely felt by those from the lowest socioeconomic groups. “Until effective ways of reducing social inequality are implemented, the best that we can hope for is timely specialist support for those developing drug related problems, such as dependency.” He concluded that problem drug use is an issue that will be with us for years and we need to build a workforce to meet the demand and ensure that these avoidable fatalities “are just that—avoided.”

09/7/21

It Doesn’t Seem Right

Back in October of 2020 Purdue Pharma signed an $8 billion-plus settlement with the U.S. Department of Justice. Purdue agreed to plead guilty to three federal criminal charges for its role in creating the nation’s opioid epidemic and shut down the company. The charges included conspiracy to defraud the U.S. government. The Daily Beast reported Purdue will admit it impeded the DEA by falsely representing it had maintained an adequate program to stop drug diversion while the company’s internal system was beginning to sound an alarm. Purdue will also admit to violating antikickback laws by inducing doctors to write more prescriptions for opioids through a paid speaker program.

Some states objected to the settlement. CNN Business reported that while the $8 billion plus agreement would be a record settlement paid by a pharmaceutical company, it is only a fraction of the cost to federal, state and local governments fighting the opioid crisis. State lawsuits throughout the country have filed claims for over $2 trillion. State attorneys general and members of Congress objected to the settlement, saying it does not hold the Sackler family and Purdue properly accountable. The Connecticut Attorney General said: “The federal government had the power here to put the Sacklers in jail, and they didn’t. Instead, they took fines and penalties that Purdue likely will never fully pay.”

If the only practical consequence of your Department’s investigation is that a handful of billionaires are made slightly less rich, we fear that the American people will lose faith in the ability of the Department to provide accountability and equal justice under the law.

Members of the Sackler family withdrew more than $10 billion from Purdue Pharma and placed it in family trusts, as the company faced growing scrutiny related to its role in the opioid epidemic. A statement from the family said, “Members of the Sackler family who served on Purdue’s board of directors acted ethically and lawfully, and the upcoming release of company documents will prove that fact in detail.”

The New York Times (NYT) reported a Purdue Pharma proposal to restructure itself as a nonprofit company was put to a vote and approved by huge majority of its creditors. The restructuring plan would protect the company from further legal action over opioids. It also includes a blanket release from civil lawsuits for the Sackler family, who argued if the plan is confirmed, they should be covered by the same release from all present and future lawsuits as their company would be. “Neither the company, nor the Sacklers, would admit to wrongdoing in connection with these lawsuits.”

Under the plan, the Sacklers would surrender control of Purdue. The company would receive a new name and be run by an independently appointed board. The Sackler family would also pay at least $4.5 billion of their personal funds over nine years. That is in addition to the $225 million from a separate civil settlement with the DOJ.

According to the plan, the reconstituted, as-yet unnamed company would fund about a half-dozen trusts, including separate ones for tribes, adults and children. Proceeds from the sales of the nonprofit’s overdose-reversing medications as well as from moderate quantities of OxyContin would continue to be pumped into these trusts.

In July 2021, NPR said fifteen states, including Massachusetts, New York, Pennsylvania, Colorado and Illinois dropped their opposition to the Purdue bankruptcy plan, according to documents filed by a court mediator. Federal bankruptcy judge Shelley Chapman said in the legal filing, “The negotiations were difficult and hard-fought, with the outcome uncertain.” Chapman was appointed to mediate a settlement the opposing states could accept. The settlement is all but certain to be finalized. In addition to members of the Sackler family, the settlement would shelter many of their associates from future opioid lawsuits.

Under the mediation agreement, Purdue agreed to release more than 30 million documents to a public repository, including private communications with lawyers. Although those documents are expected to expose the full story of the company’s and the Sackler family’s complicity in selling OxyContin, they will be shielded from any further legal action by the Purdue restructuring plan. Members of Congress have introduced legislation to close a loophole in the bankruptcy code that permitted Purdue Pharma to declare bankruptcy, while its owners—the Sacklers—did not. They will remain as one of the richest families in the U.S. Even if the legislation passes, the Purdue plan will have been long since resolved.

The hearing before the U.S. House of Representatives’ Judiciary’s Subcommittee on Antitrust, Commercial and Administrative Law took place as Democratic members of the House and Senate introduced legislation aimed at reforming areas of bankruptcy law relevant to the Sackler family and Purdue situation.

The Nondebtor Release Prohibition Act of 2021 would prohibit litigation shields for owners or insiders of bankrupt companies. Though not included in the legislation, Wednesday’s hearing also focused on potential reforms to limit the ability of bankrupt companies to select judges they think will be favorable to them.

According to Reuters, the trial over the Purdue Pharma settlement began on August 12^th and was supposed to take two weeks. The settlement is supported by all but nine states, including Connecticut (where Purdue is headquartered), California, Maryland and Washington. Washington’s attorney general said he could not in good conscience accept the terms of Purdue’s deal. “The latest settlement plan ‘allows the Sacklers to walk away as billionaires with a legal shield for life.’” Adding insult to injury, he said “they don’t even have to apologize.”

Purdue says the deal is worth more than $10 billion. If the settlement is approved, Purdue assets will be transferred to the new company. The company will be governed by a new independent board, “who will operate in a responsible and sustainable manner taking into account long-term public health interests related to the opioid crisis.” The Sackler family will have no involvement in the new company, and will end their involvement in pharmaceutical companies worldwide.

Critics of the settlement oppose the “third-party releases” that would provide legal protections to the Sacklers. The company has said that without the releases, the entire settlement, including billions of dollars for state and local opioid abatement programs, would collapse.

On September 1^st, The NYT reported the settlement agreement was provisionally approved and Purdue Pharma was dissolved. The presiding judge said the case was a B-I-T-T-E-R result, spelling out the word. He was incredibly frustrated that so much of the Sackler money was in offshore accounts. He had wished for and expected a higher settlement. The costs of further delay and the benefits of the agreement with its focus on lessening the impact of the opioid epidemic influenced his decision.

Just last month, Dr. Richard Sackler, a former president and cochairman of the board for Purdue, testified that neither the family, the company nor its products bore any responsibility for the opioid epidemic. Other Sacklers struck a more conciliatory note, saying they were horrified that a medication intended to alleviate pain had, in fact, caused pain to so many. But neither apologized nor took personal responsibility.

So, there it is. It appears that the full story of how OxyContin helped fuel the opioid epidemic will only become known when it is too late for any legal actions to be taken against individuals from Purdue Pharma or the Sackler family. The company, but no persons will be found guilty of federal crimes; no one will apologize or be held accountable for their actions. And that doesn’t seem right.

For other articles on this issue, see: “What Purdue and the Sackler Family Treasure,” “Giving an Opioid Devil Its Due,” The Tale of the OxyContin Lie,” and more.

08/17/21

The End of ENDS?

On Wednesday, June 23, 2021 the Subcommittee on Economic and Consumer Policy held its fourth hearing examining youth vaping in the US. Senator Dick Durbin and the acting FDA Commissioner, Janet Woodcock were witnesses. The FDA is in the process of determining whether e-cigarettes will be legally allowed to stay on the market. “All e-cigarette manufacturers were required to submit Premarket Tobacco Product Applications (PMTAs) to FDA by September 9, 2020, in order to legally stay on the market.” Stat News reported that Senator Durbin and other Democrats accused the FDA of inaction on the issue: “Who is the cop on the beat to whom we entrust our children? It’s the Food and Drug Administration.”

The hearing comes as the FDA begins deciding in earnest which e-cigarette manufacturers can stay on the market, as part of a congressionally mandated process. Manufacturers like Juul, Blu, and Njoy were required to submit marketing applications to the FDA in September but are allowed to stay on the market until at least September 2021, while the agency reviews those applications.

In 2018, the Surgeon General issued an advisory where he declared e-cigarette use among youth an epidemic. “We need to protect our young people from all tobacco products, including e-cigarettes.” Despite this advisory, there has been little concrete action as yet. The chair of the subcommittee said the youth vaping epidemic has continued over the past three years. “More than 20% of high schoolers vape, and 5% of middle schoolers vape.” These are the same levels that led the surgeon general to declare a youth vaping epidemic in 2018. To the FDA, he said:

No matter what your decision on Juul’s PMTA, you know that the problem does not end there. To end the youth vaping epidemic, you’ll have to deny the applications for all products with the same characteristics that made Juul so popular with a generation of children.

Federal officials had singled out Juul for fueling the epidemic because of its intentional advertising aimed at youth and the sleek design of its product, which made Juul far and away the most popular e-cigarette among young people. The company defended its products, saying it took steps to prevent youth from using them. Juul stopped distributing some flavorings to retail stores, but only after the FDA announced plans to restrict the sale of flavored e-cigarettes to young people. The Oversight Committee released internal documents from its investigation of Juul that showed the company knew its products were addictive for teens.

Included in the documents was an internal memo from a Juul-focus group in 2018 that asked the teens why the product was so attractive to kids in Middle School and High School. “Several of the young people responded that the product’s high nicotine content kept kids hooked.” Juul says it chose a high nicotine level for its pods, roughly equivalent to a pack of cigarettes, to entice adults to quit combustible cigarettes. The claim seems somewhat disingenuous, as the company began receiving complaints that its products nicotine levels were too high around one year after Juul launched in 2016.

In an October 2018 CDC press release, “Sales of JUUL e-cigarettes skyrocket, posing danger to youth,” the then director of the CDC Robert Redfield said, “The popularity of JUUL among kids threatens our progress in reducing youth e-cigarette use.” During 2016-2017, Juul Labs’ sales increased 641%, from 2.2 million devices sold in 2016 to 16.2 million devices sold in 2017. Truth Initiative, a nonprofit organization seeking to eliminate nicotine addiction, surveyed 12 to 17-year-olds in April of 2018 to assess how so many young people were getting their hands on Juul products. Seventy-four percent said they obtained Juul in a store. Fifty-two percent said they received Juul from a family member or friend. For more information on Juul, see: “JUUL Is Not a Gem,” “The Armageddon of Juul,” and “Juul’s Empty Harm Reduction Rhetoric.”

While vaping is less harmful than smoking, it still is not safe. As of February 18, 2020, the CDC reported there have been 68 deaths from EVALI—e-cigarette or vaping-associated lung injury. There were 2,807 hospitalized cases or deaths from EVALI. Laboratory data showed that vitamin E acetate, an additive in some THC-containing vaping products was strongly linked to the EVALI outbreak. The CDC recommended that people not use THC-containing e-cigarettes or vaping products. “E-cigarette, or vaping, products (nicotine- or THC-containing) should never be used by youths, young adults, or women who are pregnant.”

Michael Blaha, the director of clinical research at the John Hopkins Ciccarone Center for the Prevention of Heart Disease, shared health information about vaping in “5 Vaping Facts You Need to Know.” While vaping is less harmful than smoking, it still isn’t safe. There are many unknowns about vaping, including what chemicals are included in the vapor inhaled by users and how physical health is affected over the long term. Blaha said people need to understand e-cigarettes are potentially hazardous to their health. “Emerging data suggests links to chronic lung disease and asthma, and associations between dual use of e-cigarettes and smoking with cardiovascular disease. You’re exposing yourself to all kinds of chemicals that we don’t yet understand and that are probably not safe.”

Research suggests nicotine is just as addictive as heroin and cocaine. Many e-cigarette users get more nicotine than smokers because they can buy cartridges that have a higher concentration of nicotine. You can also increase the voltage of an e-cigarette to get a greater hit of the substance. E-cigarettes are not approved by the FDA as smoking cessation tool, even though they have been marketed as such. A study found that most people who intended to use e-cigarettes to stop smoking ended up continuing to smoke both.

According to Blaha, there are several reasons e-cigarettes are enticing to youth. Teens believe vaping is less harmful than smoking. They have a lower cost per-use than traditional cigarettes. They often have added flavorings and there is a lack of smoke from their use. “With no smell, e-cigarettes reduce the stigma of smoking.” Blaha said:

What I find most concerning about the rise of vaping is that people who would’ve never smoked otherwise, especially youth, are taking up the habit . . . It’s one thing if you convert from cigarette smoking to vaping. It’s quite another thing to start up nicotine use with vaping. And, it often leads to using traditional tobacco products down the road.

When Janet Woodcock testified before the House Subcommittee on Economic and Consumer Policy, she said protecting the youth of the US from the dangers of tobacco products was among the FDA’s most important responsibilities. “We are taking aggressive steps to make sure tobacco products are not being marketed or sold to kids.” After describing the FDA’s efforts to regulate ENDS (electronic nicotine delivery systems), and the agency’s actions to prevent youth access and use of these products, she said: “We still have much to accomplish and will continue to take strong action to protect youth and monitor the effectiveness of our actions.” Given the concerns noted here and in the linked articles, let’s hope that strong action will include the end of some ENDS products that have been clearly soliciting youthful consumers like Juul.

For more information on concerns with vaping and ENDS, see: “The Ticking Time Bomb of Vaping,” “Priming Young Adults with Vaping” and “Not the End of Smoking.”

07/27/21

A Regulated Kratom Policy

On August 31, 2016, the DEA announced its intent to temporarily place kratom into Schedule I. This meant that in the DEA’s view, there was no currently accepted medical use for kratom and a high potential for abuse. This led to an immediate and aggressive public backlash. There was a demonstration near the White House, phone calls to Congress, a petition protesting the proposed scheduling with over 100,000 signatures. On October 13, 2016, the DEA announced it would withdraw its intent to temporarily Schedule kratom because of “numerous comments from the public,” but the debate over kratom scheduling was not over just yet.

Natural Products Insider reported that in 2018 the U.S. Department of Health and Human Services, (HHS) officially rescinded the DEA’s request to classify two constituents in kratom, mitragynine and 7-hydroxymitragynine, as controlled substances. But this letter from HHS to DEA was not released to the public until January 2021, when it was made public by The American Kratom Association (AKA). The letter said, “HHS is instead recommending that mitragynine and 7-hydroxymitragynine not be controlled at this time, either temporarily or permanently, until scientific research can sufficiently support such an action.” However, the FDA is still concerned about kratom, as kratom products have been associated with significant safety concerns.

An FDA spokesman said, “While it is important to gather more evidence, data suggest that certain substances in kratom have opioid properties that expose users to the risks of addiction, abuse and dependence.” While the HHS letter did recommend against scheduling kratom, it also stated it was possible that new data and evidence could support scheduling the chemicals in kratom at some future time. “Kratom may have harmful effects, particularly when used with other drugs.” Mitragynine and 7-hydroxymitragynine have many of the properties of an opioid; and enhancing public awareness “that kratom contains molecules that may be potentially dangerous” was encouraged by the HHS.

NPR broadcasted “The Kratom Debate” on its program, Morning Edition. Linda Kline, the owner of Bumble Bee Botanicals, credited kratom with helping her with her mental health. “I went from feeling desperate and hopeless to finding an alternative where I had full control over how I felt.” She couldn’t always find a high-quality supply of kratom, so she began selling kratom herself and now has several stores in California, Idaho and Nevada.

There also was the story of Marco, who struggled with an opioid addiction in high school. He became hooked on painkillers after his dentist pulled his wisdom teeth. Eventually, when he wanted to kick his opioid addiction, he tried kratom and was eventually using multiple kratom capsules daily. During his freshman year at college, he started hyperventilating regularly. The incidents worsened, and led to seizure-like episodes and trips to the emergency room. The doctors were stumped; no one thought to test for kratom.

Marco died in his UC Davis dorm in February 2018, late on a Sunday night. The toxicology report listed “acute mitragynine intoxication” — a chemical constituent of kratom — as the cause of death.

Michael White, of the Department of Pharmacy Practice at the University of Connecticut said, “The data to support either the benefits or the harms for kratom is really, really poor.” He went on to say much of the information available comes from single-case reports. White thought scientists needed to conduct more research before the appropriate level of regulation become clear. He suggested placing it behind the pharmacy counter as with pseudoephedrine.

McLain Haddow, a spokesperson for the American Kratom association thought kratom should only be sold to adults. Haddow added that some manufacturers were adding fentanyl, heroin or morphine to their products to give users a high. “We would like vendors to register their product with the FDA and get a chemical analysis from a certified lab to ensure the only ingredient is the naturally occurring alkaloid in the kratom plant.”

Dr. Scott Steiger, the deputy medical director for an opiate treatment outpatient program said he did not know how to advise patients who wanted to try kratom. “I tell them I just don’t know enough on the basis of science to tell them whether it’s a great idea or not.” He added he’d seen people who use kratom and end up having a very hard time stopping. He doesn’t recommend self-medicating with kratom until more research is available. “We just don’t know enough about this chemical and the long-term use of it to know whether experimenting would lead to complications.”

A Wired article, “Release the Kratom,” said, “They are using the drug for everything from chronic pain relief to replacement for their morning coffee.” People also use it to improve their eye sight, clear up their skin boost their immune systems, or just get high. Some addicts use it to manage or help them get away from their addiction. Faith Day, a kratom business owner in Portland and former addict, said a third of her clientele were looking for a caffeine-free alternative to get through the day: “I’m talking soccer moms.”

According to Oliver Grundmann, who studies the effects of herbal products on the central nervous system, interest in kratom didn’t become widespread in the US and Europe until the mid 2000s. Grundmann has authored or coauthored several studies of kratom (see here and here), including “Kratom policy, The challenge of balancing therapeutic potential with public safety.” All the article’s authors are engaged in various aspects of kratom research “and it is our intention to provide a fair and balanced overview that can form the basis for informed decision on kratom policy.”

Citing data from the American Kratom Association, the authors said there were more than 1 million kratom users in the US. Given the widespread use of kratom and the extensive media attention it is receiving, the authors said policy makers need to be knowledgeable about the science of kratom. In their article, they sought to answers questions such as: should kratom be classified as an opioid; was it safe; is it effective for pain and OUD management; how serous are the abuse and addiction potentials?

Because of its ability to interact with opioid receptors, mitragynine is often referred to as an “opioid.” Yet it produces physiological, biochemical and behavioral effects that differ from classical opioids. “In light of this evidence, mitraginine and its analogs can best be described as ‘atypical opioids.’”

The authors reported that when used in its traditional context, pure kratom was unlikely to produce serious adverse effects in most users. “In fact, there have been no reported deaths attributed to kratom in Southeast Asia when used in the traditional setting as unadulterated, pure kratom leaf.” At low to moderate doses of 5 g of raw kratom leaves or less, the adverse effects generally seem mild, but can vary between persons. More troubling and serious toxicities are often associated with high dose usage or using concentrated extracts.

The lack of regulation and standardization related to the production and sale of “kratom” products are compounded by unscrupulous vendors selling kratom products adulterated with potentially toxic drugs. “Probably the most notorious example of such adulteration involved a product known as ‘Krypton’, which was touted as a very potent form of kratom.” Sold mainly in Europe, it was a factor in at least nine deaths. Detailed forensic analysis revealed that Krypton was adulterated with the synthetic opioid, O-desmethyltramadol. See “Krypton Can Kill You.”

The unregulated sale of kratom via the internet and deceitful marketing practices may have prompted some individuals to use kratom as a recreational drug. This poorly regulated market, wide distribution, and reported risks of toxicity associated with kratom use, are all likely to have encouraged regulatory agencies to suggest the removal of this product from the market.

While kratom has not been evaluated in the typical controlled clinical trials required by the FDA, many individuals believe it to be a safe and effective alternative to prescription or illicit opioids. “Nonetheless, kratom has a long history of such use that is widely accepted in the general population in Southeast Asia, where it is commonly used as an affordable substitute for street heroin or other opioids.” More than 23,000 comments to the DEA and FDA indicate many Americans have used kratom to relieve withdrawal symptoms and eliminate addictions to licit and illicit opioids.

Thus, even though we do not make the claim that kratom should be viewed as a medically proven effective and safe therapy for OUD, we believe it is warranted to take seriously the extensive user reports and analytical surveillance indicating many people are self-managing their OUD using kratom.

Regular use of kratom, especially at higher doses, can lead to tolerance and dependence. But it seems that abstinence from kratom is typically associated with milder symptomatology than abstinence from classical opioids. Even at high doses, kratom does not seem to severely depress respiration as do classic opioids. “Thus, even though kratom has some potential for abuse and dependence, several investigators have concluded that kratom has both less abuse liability and much lower risk of fatal overdose than traditional opioids.” The study authors said the potential benefits may outweigh the risks.

Kratom is widely used in the West and Southeast Asia as a relatively safe herbal supplement (traditional medicine) for the self-treatment of medical disorders, including pain and OUD. Extensive reports from kratom users, considered alongside limited basic science and clinical research studies, suggest that kratom and its constituent compounds (especially mitragynine) may in fact have beneficial pharmacological and therapeutic properties. Unfortunately, no well-controlled clinical trials have been performed to date to determine the true risks and benefits of kratom use in humans. The high monetary costs of such clinical trials greatly complicate this issue, given that sufficient intellectual property protection to justify the large capital investments necessary for formal drug approval is often challenging to obtain for natural products like kratom.

The conclusions of the authors from their analyses are: (a) kratom and its main constituent alkaloid, mitragynine may be useful for alleviating pain and managing symptoms of opioid withdrawal; (b) while kratom lacks many of the toxicities of classical opioids, there are legitimate concerns about the safety and lack of quality control over “kratom” products being sold in the US; and (c) the issues regarding the safety and efficacy of kratom and mitragynine can only be resolved by further research.

The poorly regulated market, the growing use and reported risks with kratom call for greater oversight or regulation. The suggestions noted above by McLain Haddow of the American Kratom Association are a good start. Both sides of the kratom debate agree that more scientific research is needed and the publication of “Kratom policy” described and linked above is a good start in that direction. Listing kratom as a Schedule I substance at this time will limit the ability to do quality research into the benefits and risks with kratom as it has with marijuana. The abuse and dependence liability with kratom and so-called “kratom” products is real and needs to be investigated with open eyes and not simply minimized.

It’s time for a regulated kratom policy. Let’s not repeat the mistake we made with marijuana by scheduling it before the scientific research supporting its listing can be done.

06/8/21

Never Enough and No Free Lunch

By the time she was twenty-three, it had been several years since Judith Grisel had gone twenty-four hours without a drink, pill, fix, or joint. The fun and excitement from using was long gone. “Dying slowly a day at a time was turning out to be unbearably painful.” She’d finally reached the dead end of feeling she was incapable of living either with or without mind-altering substances. But after an unexpected encounter with her father, she decided to go to rehab, became a neuroscientist and eventually wrote a book on the neuroscience and experience of addiction called Never Enough.

In the Introduction of Never Enough, she said there were two factors that motivated her desire to recover. First, she began to wonder what it would be like to be sober. “I promised myself that if I wasn’t less miserable sober than I’d been loaded, I’d go back to using.” Second, she thought she could find a cure. She admitted later on, that in early recovery, she wanted to study addiction so she could use better. “If it’s a disease, and diseases can be cured, and I can cure it, then maybe I can still use.”

But as her knowledge and understanding grew, she discovered she had something to focus on that was not about using. Her growing knowledge about addiction also gave her more compassion for herself and others. She recognized she did not initiate drug use with a blank slate. “I started out with certain tendencies that make drugs for me so valuable and important, that really the courage and perseverance I’ve demonstrated over thirty years, both trying to study this and stay clean and sober, is something that I’m proud of.” She added that character traits that facilitated her addiction—bottomless curiosity, a willingness to take risks, and perseverance—contributed to the successes she’d had as a neuroscientist.

More than anything else, seeking and acquiring knowledge about drugs, addiction, and the brain have given me compassion for the desperate plight of people like me. The understanding I’ve gained has helped me stay clean by informing better choices. My hope is that by illuminating the seeming insanity of colluding in habits that are not only joyless but lethal, this book will contribute to a path of freedom for others.

When Never Enough was first published in 2019, Judith Grisel was interviewed on the NPR program, “Fresh Air.” She said during her interview that she was always interested in the mechanisms of things. She thought if she studied the biological basis of addiction and understood it, perhaps she could “fix” it. She had moments, one after another, of learning things that explained her experiences when using drugs. “There is a common sub strait for all addictions, in neurochemistry in dopamine pathways. And it made perfect sense to me that my dopamine pathways were especially attuned to hear signals from drugs and other things.”

One of the things she learned was that the more you use a drug to change the way you feel, the more your brain produces the exact opposite state. This is the case for every single drug. If you take a drug to feel awake, you will produce lethargy. If you take a drug to feel relaxed, you’ll produce anxiety and tension. A naive user will get a big experience of the drug. “But a regular user feels about normal.”

If you are familiar with 12 Step recovery, you have probably heard the saying; “A drug is a drug, is a drug.” While other recovering addicts are not behavioral neuroscientists like Judith Grisel, they are essentially saying the same thing here. In Never Enough, Grisel said there are three laws in psychopharmacology that apply to all drugs. First, all drugs act by changing the rate of what is already going on in the brain. “They only work by interacting with existing brain structures.”

It follows that drugs can either speed up or slow down ongoing neural activity—and that’s it. Every drug has a chemical structure (a three-dimensional shape) that is complementary to certain structures in the brain and produces its effects by interacting with those structures.

The second law states all drugs have side effects. This happens because drugs do not target specific cells or circuits like neurotransmitters do. Drugs act at all accessible targets, meaning “they act whenever they encounter a receptive structure.” Drugs like nicotine, THC and heroin are called exogenous drugs, meaning they originate outside the body. They work because they mimic endogenous neurotransmitters. Endogenous means they are made inside your body.

For example, the neurotransmitter serotonin modulates mood, cognition, learning, memory, and other physical processes. It is involved with sleep, aggression, sex, and eating. Serotonin targets particular cells at particular times, depending on whether or not it is time to sleep, fight, etc. In contrast, if you take an SSRI, a selective serotonin reuptake inhibitor, it will influence all these behaviors at the same time, producing side effects in addition to potentially influencing your mood.

The third law is particularly important to addiction. It concerns how the brain responds to drugs, not how drugs act on the brain. “The brain is not just a passive recipient of drug actions but responds to the effects of the drugs.” In other words, there is a bidirectional, two-way street kind of relationship between a drug and the brain. “Repeated administration of any drug that influences brain activity leads the brain to adapt in order to compensate for the changes associated with the drug.” This is called adaptation.

For the brain, the difference between normal rewards and drug rewards is like the difference between someone whispering into your ear and someone shouting into a microphone. Just as we turn down the volume on a radio that is too loud, the brain of someone who misuses drugs adjusts by producing fewer neurotransmitters in the reward circuit, or by reducing the number of receptors that can receive signals. As a result, the person’s ability to experience pleasure from naturally rewarding (i.e., reinforcing) activities is also reduced. See the following illustration.

This reduction of receptors takes time to return to a pre-drug use homeostasis and in some cases may not be able to return completely. That is why a person who misuses drugs eventually feels flat, without motivation, lifeless, or depressed; they are unable to enjoy things that used to be pleasurable for them. Now, the person needs to keep making drugs to feel normal or experience a normal level of reward—which only makes the problem worse. The person will also need to take larger amounts of the drug to produce their high—an effect known as tolerance. Getting high is increasingly short-lived; and the purpose in using becomes to put off withdrawal.

The terrible truth for all those who love mind-altering chemicals is that if the chemicals are used with regularity, the brain always adapts to compensate. . . . The brain’s response to a drug is always to facilitate the opposite state; therefore, the only way for any regular user to feel normal is to take the drug. Getting high, if it occurs at all, is increasingly short-lived, and so the purpose of using becomes to stave off withdrawal.

This maxim applies to every effect of any drug that impacts the brain. At first, drugs produce good feelings because when they reach the brain, they impact the nucleus accumbens and other brain structures related to experiencing pleasure. But the brain is designed to return to its homeostatic “set point.” So, it counteracts the flood of dopamine released by the drug, which is interpreted as pleasure or the possibility of pleasure.

This is the driving force and curse of regular drug users. It results in an urge to use and reinforces the destructive cycle that underlies habitual drug use. With repeated exposure to the same stimulus over time, there are smaller and smaller changes in dopamine. Eventually, there is essentially no change in mesolimbic dopamine when exposed to a favored drug. But withholding it leads to a big drop in dopamine levels, which we experience as “a feeling of disappointment and craving.” The disappointment and craving experience anticipates that withdrawal is not far behind. Ultimately, according to Grisel, the most profound law of drug use is there is no free lunch.

Faith Seeking Understanding

Charles Sigler, D.Phil.

Category Archives: Addiction & Recovery