11/28/23

Counterfeit Pills, Snapchat and Overdose Deaths

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WPVI-TV, channel 6 in Philadelphia told a story about a new legal battle over drugs available on social media. More than 60 families are suing Snapchat, arguing the overdose deaths of their children were due to the social media app. They are demanding changes to protect their children, claiming they died after buying illegal drugs sold by dealers on the app. One parent said, “Snapchat is the largest open-air drug market we have in the United States when it comes to our kids.”

CNN reported the number of drug overdose deaths is still increasing, but seems to be slowing. New estimates from the CDC estimates were 112,024 people died from a drug overdose in the 12-month period ending in May of 2023. This was a 2.5% increase over the 12-month period ending in May of 2022 (109,261). Dr. Katherine Keyes, a professor of epidemiology, said, “There were extraordinary increases in 2020 and 2021 that have started to flatten out in 2022 – now going into 2023. They’re not declining yet. But the pace of the increase is certainly slowing.”

However, certain states have seen steep increases in overdose deaths in comparison to national totals. For example, overdose deaths in Washington increased more than 37%, from 2,373 to 3,254. Fentanyl and other synthetic opioids were involved in most overdose deaths, followed by psychostimulants like methamphetamine. Washington’s dramatic increase in overdose deaths may have been fueled by the availability of counterfeit pills, which we will look at below.

A CDC report said more than 1 million people died between 1999 from and 2021 of a drug overdose. Synthetic opioids other than methadone seem to be the main driver of drug overdose deaths. “Nearly 88% of opioid-involved overdose deaths involved synthetic opioids.” Opioid were involved in 75.4% of all drug overdose deaths.

A NCHS data brief released in December of 2022 indicated drug overdose deaths were stable from 2006 through 2013, but then increased from 13.8 per 100,000 in 2013 to 32.4 in 2021. From 2020 to 2021, the rate increased 14% from 28.3 to 32.4 per 100,000. For each year from 2001 through 2021, the rate for males was higher than females. Notice from the following figure the dramatic increase in overdose deaths that begins in 2019, the year before the COVID pandemic.

Despite the concerns of parents with Snapchat making it easy for dealers to connect with teenagers seeking drugs, there were four other age groups with higher rates of overdose deaths.  Among adults aged 25 and older, the rate of drug overdose deaths was higher in 2021 compared to 2020. The rates were highest for adults aged 35-44 (53.4 and 62.0 per 100,000 respectively) and lowest for people 65 and older. See Figure 2 below.

The drug overdose deaths involving synthetic opioids other than methadone (fentanyl, fentanyl analogs, and tramadol) increased at different rates from 2001 through 2021. Natural and semisynthetic opioid overdose deaths (i.e., oxycodone and hydrocodone) increased from 1.2 to 3.5 per 100,000 in 2010 and then leveled off, reaching 4.0 per 100,000 in 2020 and 2021. The rate of overdose death involving methadone increased from 0.5 in 2001 to 1.8 in 2006. Then it decreased through 2019 to 0.8, and remained stable through 2021 (1.1). “Of the drugs examined, only drug overdose deaths involving heroin had a lower rate in 2021 than in 2020 (2.8 and 4.1, respectively).” See figure 4 below.

Overdose deaths from cocaine and stimulants were also on the rise. Cocaine-related overdose deaths was a bit of a roller coaster ride, increasing from 1.3 per 100,000 in 2001 to 2.5 in 2006, then decreasing to 1.5 in 2001, and then increasing to 7.1 in 2021. “The rate in 2021 was 22% higher than in 2020 (6.0).” The rate of overdose deaths involving psychostimulants (i.e., amphetamine, methamphetamine and methylphenidate) increased from 0.2 in 2001 to 0.5 in 2005, remaining stable through 2008. Then it increased from 0.4 in 2008 to 10.0 in 2021. The rate in 2021 was 33% higher than the rate in 2020 (7.5). See Figure 5 below.

Drug overdose deaths have risen fivefold over the past 20 years. The rate for males increased from 39.5 to 45.1 and the rate for females increased from 17.1 to 19.6, from 2020 to 2021. For both sexes, the highest rates were for adult between 35 and 44. The rates of drug overdose deaths involving opioids and stimulants increased from 2020 to 2021.

Counterfeit Pills

One disturbing trend that seems to be driving that increase in overdose deaths is the evidence of counterfeit pill use in the U.S. In a September CDC Morbidity and Mortality Report (MMWR), the CDC said these pills are not manufactured by pharmaceutical companies, but are made to look like legitimate drugs, frequently oxycodone and alprazolam (Xanax). Counterfeit pills often contain illicitly manufactured fentanyls and illicit benzodiazepines like bromazolam, etizolam and fluaprazolam. They increase the risk of overdose by exposing individual users to drugs they did not intend to use and did not know they were in the pills they were buying.

The overall increase of overdose deaths with evidence of counterfeit pill use increased from 2% to 4.7%, driven by an increase from 4.7% to 14.7% in Western states. More than half of overdose deaths with evidence of counterfeit pills (55.8%) occurred in Western states such as Washington. See the following table reproduced from data in Table 1 of the above CDC MMWR report.

The report had these key findings. First, the overall percentage of overdose deaths with evidence of counterfeit pills remained under 6%, but more than doubled from 2.0% in the third quarter of 2019 (July-September) to 4.7% in the fourth quarter of 2021 (October-December). The percentage more than tripled in Western states. Second, the percentage of deaths with evidence of counterfeit pills using illegally manufactured fentanyl (IMF) was more than double the percentage of deaths without evidence of counterfeit pill use.

Evidence of counterfeit pill use more than tripled in western jurisdictions, indicating IMFs, which are frequently present in counterfeit pills, are infiltrating drug markets in western U.S. states. Historically, white-powder IMFs have been less prevalent in western states because of difficulty mixing with predominantly black tar heroin prevalent in that region. The highest percentages of deaths with evidence of counterfeit oxycodone use (both alone and with counterfeit alprazolam) were in western jurisdictions, whereas nearly one half of deaths with evidence of counterfeit alprazolam use only were in southern jurisdictions. This finding suggests that exposure to different types of counterfeit pills and drugs might vary by region. Prevention and education materials that incorporate local drug seizure data and information about regional drug markets might be particularly effective at highlighting relevant counterfeit pill types and reducing deaths.

Those who died from counterfeit pills were significantly younger and more often Hispanic. Counterfeit pills have been marketed towards younger persons, where they may also exhibit more risk-taking behaviors than do older persons. The higher percentage of Hispanic persons could reflect the has implications for access to and use of prevention messaging materials and harm reduction services. “It is important to ensure that prevention messaging and harm reduction outreach are tailored to younger persons and the Hispanic population to address potential engagement, language, or other barriers.”

The DEA reported their lab testing revealed that 4 out of 10 counterfeit pills contain at least 2 mg of fentanyl, a potentially lethal dose. Criminal networks are mass producing counterfeit pills and marketing them as legitimate prescription pills. They’re often sold on social media and e-commerce platforms, which make them widely available to anyone. In 2021, the DEA seized 20 million fake pills, more than the 2 previous years combined. They’ve been identified in all 50 states.

In “Overdosing,” I wrote of the overdose problem as it existed in 2016, before fentanyl, counterfeit pills and Snapchat had become part of the problem. There I referred to “Melanie,” the first person I worked with who eventually became a heroin overdose statistic in the late 1980s. In that article is a map of Pennsylvania showing the drug-related overdose deaths by county in 2014. Philadelphia County even then had the most reported deaths, followed by Allegheny County, where I live. Legislation allowing first responders to carry naloxone to reverse an overdose had just been passed. Let’s continue to fight against the everchanging and adapting drug trade and never forget those who were taken too soon by overdose like Melanie.

01/19/21

Co-Occurring COVID Surges

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We’re now all getting ready to queue up for one of the COVID vaccines. But while our attention was on COVID surges and the political circus, there were also a surge of drug overdose deaths. The CDC reported in the twelve months ending in May 2020, there were over 81,000 drug overdose deaths in the US, the largest number of drug overdoses ever for a 12-month period. After declining 4.1% from 2017 to 2018, the number of overdose deaths increased 18.2% from June 2019 to May 2020. The increases appear to have accelerated during the COVID-19 pandemic.

The recent increase in drug overdose deaths began in 2019 and continued into 2020, before the declaration of the COVID-19 National Emergency in March. However, provisional overdose death estimates indicate that from the end of February 2020 to the end of March 2020 there was an increase of 1,511 deaths. From the end of March 2020 to the end of April 2020 there was an increase of 2,146 deaths. And from the end of April 2020 to the end of May 2020 there was an increase of 3,388 deaths. These totals were the largest monthly increases since provisional 12-month estimates began to be calculated in January 2015. See the figure below taken from the CDC Health Alert Network report.

Not surprisingly, synthetic opioids were the main driver of the increases in overdose deaths. “State and local health department reports indicate that the increase in synthetic opioid-involved overdoses is primarily linked to illicitly manufactured fentanyl.” Not all of the reporting jurisdictions (the fifty states plus the District of Columbia and New York City) had available data on synthetic opioids. Of the 38 jurisdictions with available synthetic opioid data, 37 reported increases in synthetic opioid overdose deaths for the time period (June 2019 to May 2020); 18 increases were greater than 50% and 11 increases were between 25% and 49%. See Figure 3 in the above linked CDC report for information on which jurisdictions were not included.

Historically, deaths involving illicitly manufactured fentanyl have been concentrated in the 28 states east of the Mississippi River, where the heroin market has primarily been dominated by white powder heroin. In contrast, the largest increases in synthetic opioid deaths from the 12-months ending in June 2019 to the 12-months ending in May 2020 occurred in 10 western states (98.0% increase). This is consistent with large increases in illicitly manufactured fentanyl availability in western states and increases in fentanyl positivity in clinical toxicology drugs tests in the West after the COVID-19 pandemic. Increases in synthetic opioid overdose deaths were also substantial in other regions: 12 southern states and the District of Columbia (35.4%), 6 midwestern states (32.1%), and 8 northeastern states and New York City (21.1%) (Figure 3).

Overdose deaths from cocaine increased by 26.5% from June 2019 to May 2020. The recent deaths are due primarily to overdose deaths involving both cocaine and synthetic opioids. In contrast, overdose deaths from psychostimulants like methamphetamine have been increasing without synthetic opioid co-use. The rate of increase was faster than overdose deaths involving cocaine and is now greater than the number of cocaine-involved deaths. There was a projected increase of 34.8% of overdose deaths from psychostimulants from June of 2019 to May of 2020.

During a recent webinar, “COVID-19 and Its Impacts on Substance Abuse,” a past president of the American Medical Association (AMA) said it was imperative that we continue to talk about health issues other than COVID 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.” The AMA said that science, evidence and compassion must continue to guide patient care and policy change as the nation’s opioid epidemic develops into a more alarming and convoluted drug overdose epidemic.

The federal government has eased regulations that make it easier for doctors to treat patients with substance use disorder during the pandemic. But it is not clear that all states will take advantage of these relaxed policies. The DEA has issued guidance that allows practitioners to prescribe buprenorphine to new patients with opioid use disorder after a telephone evaluation.  A SAMHSA (Substance Abuse and Mental Health Services) policy allows stable methadone patients to obtain up to 28 days of take-home medication. “With social distancing recommendations and inconsistent public transportation availability, this policy assists patients that might not be able to visit an opioid treatment program on a daily basis.”

In the midst of COVID surges and the steady rise of drug overdose deaths, there is another COVID-related escalation happening with mental health symptoms in the U.S. and around the world. The 2020 Commonwealth International Health Policy Survey found that one-third of U.S. adults reported experiencing stress, anxiety and great sadness that was difficult to cope with since the COVID outbreak started. Americans were more likely than people in other countries to report mental health concern. Past research showed that Americans were already more likely to experience emotional distress, yet it seems the pandemic has contributed to higher rates of emotional distress in several countries. “The negative impact of COVID-19 on mental health has been immediate, and the pandemic is certain to have long-term effects in every country it has touched.”

Fifty-six percent of U.S. adults who reported experiencing any negative economic consequences of the pandemic also reported having mental health distress. The pandemic’s economic toll has contributed to higher levels of mental distress in other places as well. In all five countries for which reliable estimates could be calculated, people who said they experienced any type of economic insecurity since the start of the outbreak were several times more likely to also report stress, anxiety, and great sadness that was difficult to cope with alone.

The New York Times reported there is growing evidence that a small number of COVID patients with no history of mental health problems are developing severe psychotic symptoms weeks after contracting the virus. A British study published in The Lancet found 10 individuals out of 153 patients hospitalized with COVID-19 had new-onset psychosis. A Spanish study published in the journal Psychiatry Research also found ten individuals with new-onset psychotic episodes in COVID-19 patients. In COVID-related social media groups, medical professionals discussed seeing patients with similar symptoms in the Midwest, Great Plains and other places in the U.S. Neurological, cognitive and psychological symptoms could emerge even in patients who did not have serious lung, heart or circulatory problems.

A 36-year-old nursing home employee in North Carolina who became so paranoid that she believed her three children would be kidnapped and, to save them, tried to pass them through a fast-food restaurant’s drive-through window.A 30-year-old construction worker in New York City who became so delusional that he imagined his cousin was going to murder him, and, to protect himself, he tried to strangle his cousin in bed.A 55-year-old woman in Britain had hallucinations of monkeys and a lion and became convinced a family member had been replaced by an impostor.

Experts speculate that these brain-related effects may be linked to either vascular problems or surges of inflammation caused by the disease process; Another possibility is the body’s immune system response to the coronavirus. Persistent immune activation is a leading explanation for memory problems and what has become known as “COVID brain fog.” Some post-COVID psychosis patients needed weeks of hospitalization while doctors tried different medications. There have been past reports of post-infectious psychosis and mania with other viruses, including the 1918 flu, SARS and MERS.

We don’t know what the natural course of this is . . . Does this eventually go away? Do people get better? How long does that normally take? And are you then more prone to have other psychiatric issues as a result? There are just so many unanswered questions.

While we appropriately focus our attention on COVID, let’s not forget about the growing problem with drug overdoses and not neglect the emergence of post-COVID psychosis. As the AMA exhorted, science, evidence and compassion must guide us in addressing the COVID pandemic, the overdose epidemic and the concurrent rise of mental health concerns.

For other articles on drug overdoses or anxiety in the midst of COVID, see “Drug Overdose Deaths: In the Shadow of COVID-19” and “An Epidemic Emerging from the Pandemic?

07/21/20

Drug Overdose Deaths: In the Shadow of COVID-19

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Over the last several months news of the COVID-19 pandemic has flooded the U.S. news media. Fears of a resurgence of positive cases and deaths from the virus are the new concern as states relax social distancing guidelines. When you look at the CDC website tracking total cases and deaths due to COVID-19, a clear geographic pattern is evident. California, Illinois, Michigan, Pennsylvania, New York, New Jersey and Rhode Island all have reported 40,000 or more cases, while Alaska, Hawaii, Montana, Wyoming and Vermont have reported less than 1,000 cases.  Unfortunately, worry over COVID-19 has driven concern over drug overdose deaths as a public health concern from the consciousness of most people.

The CDC also reported a pattern to its data on overdose deaths in a “National Vital Statistics Report,” that illustrated the most lethal drug by geographic region. Overall, the drug most frequently involved in overdose deaths in the U.S, was no surprise; it was fentanyl. It accounted for approximately 39% of all drug overdose deaths. When the data is grouped regionally, fentanyl was the drug most frequently involved in overdose deaths east of the Mississippi and methamphetamine was the drug most frequently involved west of the Mississippi. Region 7, consisting of Nebraska, Iowa, Missouri and Kansas broke this pattern in reporting fentanyl as the drug most frequently involved in overdose deaths. See the following map for fentanyl taken from the October 2019 edition of the “National Vital Statistics Reports.”

The top 15 drugs belonged to several drug classes: opioids (fentanyl, heroin, hydrocodone, methadone, morphine, oxycodone, and tramadol), benzodiazepines (alprazolam, clonazepam, and diazepam), stimulants (amphetamine, cocaine, and methamphetamine), an antihistamine (diphenhydramine) and an anticonvulsant (gabapentin). Nationally, 38.9% of drug overdose deaths involved fentanyl (including fentanyl metabolites, precursors, and analogs), 22.8% involved heroin, 21.3% involved cocaine, and 13.3% involved methamphetamine. Alprazolam, oxycodone, and morphine were each involved in 6.9%–9.5% of the drug overdose deaths in 2017, while methadone, hydrocodone, diphenhydramine, clonazepam, diazepam, gabapentin, amphetamine, and tramadol were each involved in less than 5.0%.

Among the opioids, fentanyl, heroin, hydrocodone (Vicodin) and oxycodone (OxyContin) have been getting the lion’s share of the overdose press. But notice that methadone, used as an opioid maintenance drug, and tramadol also made the list. Benzodiazepines like alprazolam (Xanax), clonazepam (Klonopin) and diazepam (Valium) have been a growing, and hidden misuse and overdose problem, overshadowed by opioids like heroin and fentanyl. Gabapentin (Neurontin) likely became an overdose drug because of its use as a cheap way to potentiate an opioid high.Six drugs were found among the top ten most frequently involved drugs in all 10 of the Department of Health and Human Services (HHS( public health regions: alprazolam, cocaine, fentanyl, heroin, methadone and oxycodone. See the following table listing the top fifteen drugs most frequently involved in overdose deaths.

Commenting on the CDC data in the “National Vital Statistics Report” for ABC News, Holly Hedegaard, an epidemiologist and co-author of the report, noted how the drug problem was not the same across the country. “What’s interesting is that the patterns are different across the U.S.”

Zachery Dezman, an assistant professor of emergency medicine, thought the regional variations were the end product of cultural influences. Methamphetamine use beginning in California could account for the drug’s strong regional presence. “Like all culture, it varies from region to region and is a result of history, demand, law enforcement.” Although methamphetamine can be made cheaply, using material found on most farms, it produces a large amount of toxic waste. “So methamphetamines are more often produced in rural or isolated areas where it is easier to hide from the authorities.”

Dezman’s assessment may have been true in the 1990s, but there seem to be other factors influencing the geographic divide noted above. Writing for The Fix, Seth Ferranti indicated that 90% of the methamphetamine in the U.S. comes from Mexico, primarily manufactured in super labs by drug cartels. The Mexican labs, like the TV show Breaking Bad, are making a very pure, relatively cheap meth. Local suppliers then “cut” the meth with cheaply produced fentanyl in order to sell more of it at a lower expense. Brandon Costerison, a project manager for the National Council on Alcoholism and Drug Abuse said: “It’s a lot stronger, so we’re seeing a lot more psychosis, but we’re also seeing it being tainted with fentanyl, which is leading to more deaths.”

According to the 2018 National Drug Threat Assessment, the methamphetamine sampled in the second half of 2017 averaged 96.9% pure. The price per gram of meth was $70. The purity had increased 6%, while the price decreased 13.6%. Most of the Mexican transnational criminal organizations (TCOs) or drug cartels are involved in trafficking methamphetamine, which has led to increased competition between the cartels. The authors of the 2018 National Drug Threat Assessment speculated this competition led the Mexican TCOs to try moving into new territories and experiment with novel smuggling methods, such as the use of drones, in attempts to increase their methamphetamine customer base.

Though not favored by traffickers due to their noise, short battery life, and limited payload, advances in technology may make this method more feasible. As the technology advances and addresses these shortcomings, drones may prove more attractive to smugglers, which in turn may increase their prevalence as a smuggling technique across the border.

Currently methamphetamine laboratory seizures in the U.S. are at the lowest level in 15 years and domestic production is at its lowest point since 2000.  From a high of 23,703 in 2004, there were 3,036 seizures in 2017. Between 2012 and 2017, the number of seized domestic meth laboratories decreased by almost 78%. This can be attributed, at least partly, to the Combat Methamphetamine Epidemic Act (CMEA), which was signed into law on March 9, 2006 to regulate over-the-counter sales of methamphetamine precursors like ephedrine and pseudoephedrine. But it left a supply hole the Mexican cartels were happy to fill.

The number of deaths due to psychostimulants continues to increase dramatically. According to the CDC, methamphetamine drug poisoning deaths are included under the broader category of psychostimulants, which include MDMA, amphetamine and caffeine. While the value changes yearly, recently 85 to 90% of the drug poisoning deaths reported under psychostimulants mentioned methamphetamine on the death certificate. “According to the CDC, in 2016 there were 7,542 psychostimulant drug poisoning deaths in the United States, representing a 32 percent increase from 2015, and a 387 percent increase since 2005.” See the following figure from the 2018 National Drug Threat Assessment. 

Despite the growth of methamphetamine use, for people who use the drug, treatment options are slim. Currently there is no FDA-approved medication for methamphetamine use disorder, but there seems to be some promising results with naltrexone. Available as a pill or an extended release injection (Vivitrol), naltrexone is used to prevent a relapse with opioid use and it suppresses the euphoria and pleasurable sensations from drinking alcohol. There have been some studies of naltrexone as a treatment for methamphetamine use disorder.

Ray et al published a double blind, placebo-controlled study of naltrexone with individuals meeting DSM criteria for methamphetamine abuse or dependence. The results indicated that naltrexone reduced the pleasurable effects of the drug as well as cravings. The lead author of the study, Lara Ray told ScienceDaily: “The results were about as good as you could hope for.” She has done several studies on the effectiveness of naltrexone for methamphetamine addiction, including one on how executive function moderated naltrexone effects on methamphetamine-induced craving.

Naltrexone significantly reduced the subjects’ craving for methamphetamine, and made them less aroused by methamphetamine: Subjects’ heart rates and pulse readings both were significantly higher when they were given the placebo than when they took Naltrexone. In addition, participants taking Naltrexone had lower heart rates and pulses when they were presented with their drug paraphernalia than those who were given placebos.

NPR published an article noting how a woman successfully used naltrexone to help her stop using methamphetamine. She had used drugs like cocaine for years, since she was a teenager. But when she tried crystal meth, she said she was hooked from the first hit. “It was an explosion of the senses. It was the biggest high I’d ever experienced.” She went from 240 pounds to 110. She also lost custody of her children. She said three to four hours after she took the first naltrexone pill, she felt better. After taking the second pill, her withdrawal symptoms lessened.

Nancy Beste, the certified addiction counselor and physician’s assistant who treated the woman, has tried naltrexone with about 16 patients who use methamphetamine. It appeared to help reduce cravings in about half of them. She also treats individuals with opioid addiction and all her patients do counseling in conjunction with medication-assisted treatment. Her treatment goal is to eventually wean them off the medications. Unlike buprenorphine and methadone, naltrexone is not a controlled substance with its own addiction potential. In my opinion, that makes it a promising medication assisted treatment (MAT) for methamphetamine.

Drug overdose deaths did not just disappear when COVID-19 arose. The CDC reported 128 people die every day from an opioid overdose. Although the number of drug overdose deaths decreased by 4% from 2017 to 2018, it was still four times higher than in 1999. Prescription-involved deaths had increased by 13.5% while heroin-involved deaths decreased by 4%. Synthetic opioid-involved deaths, excluding methadone, increased by 10%. Methamphetamine-involved deaths accounted for approximately 11% of the of the number of drug overdose deaths in 2018. The COVID-19 pandemic may have overshadowed the opioid epidemic, but it didn’t stop it.

I’ve written about all these drug classes and the potential they have for abuse. For starters, see “Through the Fentanyl Looking Glass,” “Doubling the Risk of Overdose,” and others on opioids. Also see “Global Trouble with Tramadol”, “Gabapentinoids Perpetuate Addiction” and “The Evolution of Neurontin Abuse” for more on the problems with gabapentin or tramadol. See “Are Benzos Worth It?” “It Takes Away Your Soul” and “Dancing with the Devil” on concerns with benzodiazepines. Search on the website for the drug you are interested in reading more about in other articles.

11/5/19

Ticking Time Bomb of Speedballing

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What do the following celebrities have in common: John Belushi, Chris Farley, Phillip Seymour Hoffman, and River Phoenix? Their deaths were attributed to speedball use, a combination of cocaine and heroin or morphine. Speedballs may also combine other pharmaceutical opioids, benzodiazepines or barbiturates along with stimulants, as it seems was the case with the death of Phillip Seymour Hoffman. The combination of stimulant and depressant drugs suppresses the usual negative side effects of each class of drugs, which can lead to misjudging the tolerance or intake of one or both drugs. “Due to the countering effect of the cocaine, a fatally high opioid dose can be unwittingly administered without immediate incapacitation, thus providing a false sense of tolerance until it is too late.”

Combining stimulants and opiates dates back at least to Sigmund Freud, who unsuccessfully attempted to counteract a friend’s morphine addiction with cocaine. Freud later acknowledged he may have hastened his friend’s death by “trying to cast out the devil with Beelzebub.” Nevertheless, Freud continued his personal use of cocaine despite his failed attempt to counter his friend’s morphine addiction. Several scholars have debated whether or not Freud’s use of cocaine influenced his developing theories, especially their emphasis on sex. For more information on Freud and his cocaine use, see “Sigmund Freud was a Cocaine Evangelist and Addict.”

The polysubstance misuse of stimulants and opioids has not received much media attention, but in the evolving nature of the opioid crisis that may be changing. The CDC recently published the results of an investigation of drug overdose deaths with cocaine and psychostimulants in the US between 2003 and 2017. In 2017 there were 70,237 drug overdose deaths, of which nearly a third (32.9%) involved cocaine, psychostimulants or both. Nearly three quarters of cocaine-involved deaths and about one half of the psychostimulant-involved deaths involved at least one opioid. Between 2006 and 2012 there was a decrease in overall cocaine-involved death rates that seems to have paralleled a decline in cocaine supply, but they began to increase again in 2012 (See the following figures).

Drug overdoses continue to evolve along with emerging threats, changes in the drug supply, mixing of substances with or without the user’s knowledge, and polysubstance use. In addition, the availability of psychostimulants, particularly methamphetamine, appears to be increasing across most regions. In 2017, among drug products obtained by law enforcement that were submitted for laboratory testing, methamphetamine and cocaine were the most and third most frequently identified drugs, respectively. Previous studies also found that heroin and synthetic opioids (e.g., illicitly-manufactured fentanyl) have contributed to increases in stimulant-involved deaths. Current findings further support that increases in stimulant-involved deaths are part of a growing polysubstance landscape. Although synthetic opioids appear to be driving much of the increase in cocaine-involved deaths, increases in psychostimulant-involved deaths have occurred largely without opioid co-involvement; however, recent data suggest increasing synthetic opioid involvement in these deaths.

Among the 70,237 overdose deaths in 2017, 13,942 (19.8%) involved cocaine and 10,333(14.7%) involved psychostimulants. Death rates increased from 2016 to 2017 in both drug categories across demographic categories such as sex and race. Male overdoses involving cocaine increased 31.9%. Male overdoses involving psychostimulants increased 32.4%. Female overdoses involving cocaine increased 38.9%. Female overdoses involving psychostimulants increased 35.7%.

White, non-Hispanic overdoses involving cocaine increased 35.3%. White, non-Hispanic overdoses involving psychostimulants increased 40.0%. Black, non-Hispanic overdoses involving cocaine increased 36.1%. Black, non-Hispanic overdoses involving psychostimulants increased 33.3%. Hispanic overdoses involving cocaine increased 25.0%. Hispanic overdoses involving psychostimulants increased 33.3%.

Preliminary data for 2018 suggests continuing increases in drug overdose deaths. Given the rise in deaths involving cocaine and psychostimulants “and the continuing evolution of the drug landscape,” the authors called for a rapid, multifaceted and broad approach that included both surveillance efforts and prevention and response strategies. The mixture of opioids in stimulant-involved overdoses underscored the importance of continued opioid overdose surveillance and prevention measures, including the expansion of naloxone availability. The CDC is expanding its drug overdose surveillance to include stimulants. And it is implementing evidence-based opioid prevention efforts such as improving the ability for users to access care and collaborations with public health and public safety organizations.

The increase of stimulant deaths without opioid involvement requires efforts to identify and improve access to care for persons who only use stimulants as well. The authors also suggested implementing upstream prevention efforts focusing on shared risk with both opioids and cocaine. The Fix cited comments by Hans Brieter, a psychiatry professor at Northwestern University, on how cocaine is thought of as a safer drug to use by many people today. “There’s been a lot of bad press about other drugs.” Younger people today didn’t see firsthand the 1970s dangers of cocaine, he said, so they mistakenly believe it to be the safer drug. Increased efforts towards protective factors that address substance use/misuse and improve risk reduction (“don’t use alone”) should be made as well.

The concluding sentence of the CDC Report called for collaboration between the community and public health and safety organizations, in order to understand the local drug scene and reduce its risks to users of both drugs. “Continued collaborations among public health, public safety, and community partners are critical to understanding the local illicit drug supply and reducing risk as well as linking persons to medication-assisted treatment [MAT] and risk-reduction services.” Here we may be seeing a peek under the hood at what the authors fear the most with their suggested linking to MAT, namely the increasing synthetic opioid involvement in cocaine-involved or psychostimulant overdose deaths. Remember that speedballing mixes a stimulant with a depressant. Due to the offsetting effects of the two drugs, a fatal amount of an opioid could be used without a realization of the danger until it’s too late.

06/29/18

Through the Fentanyl Looking Glass

Tenniel sketch from “Alice through the looking glass” 1871; in the public domain

A May 1, 2018 research letter in JAMA, “Changes in Synthetic Opioid Involvement in Drug Overdose Deaths,” found that the involvement of synthetic opioids in overdose deaths increased from 14.3% of opioid-related deaths in 2010 to 45.9% in 2016. “Among synthetic opioid-related overdoes deaths in 2016, 79.7% involved another drug or alcohol.” The most common substances were another opioid (47.9%), heroin (29.8%), cocaine (21.6%), prescription opioids (20.9%), benzodiazepines (17.0%), alcohol (11.1%), psychostimulants (5.4%) and antidepressants (5.2%). “Lack of awareness about synthetic opioid potency, variability, availability, and increasing adulteration of the illicit drug supply poses substantial risks to individual and public health.”

Widespread public health messaging is needed, and clinicians, first responders, and lay persons likely to respond to an overdose should be trained on synthetic opioid risks and equipped with multiple doses of naloxone. These efforts should be part of a comprehensive strategy to reduce the illicit supply of opioids and expand access to medication-assisted treatment for opioid addiction.

This was the first time synthetic opioids surpassed prescription opioids and heroin as the primary cause of opioid overdose-related deaths. The analysis was limited because 15% to 25% of the death certificates failed to specify which type of drug(s) were involved in the overdose. In “Synthetics now killing more people than prescription opioids, report says,” CNN quoted the lead author of the JAMA report as saying, “So the actual numbers are likely higher.” He added that the findings track closely to the increased availability of illicit synthetic opioids coming into the US.

A senior staff attorney for the nonprofit Drug Policy Alliance commented how synthetic opioids are easier to manufacture than heroin. She also said China was the primary source for illicit fentanyl. “ Illicitly manufactured fentanyl is almost exclusively made in China. . . . It’s then shipped, broadly speaking, to Mexico, where it’s added to the heroin supply before it enters the United States as a cost-saving measure.”

An added concern is while initially synthetic opioids were mixed with heroin, now it’s “mixed with cocaine, methamphetamines and other substances of abuse.” There are also counterfeit tablets containing fentanyl that are made to look like prescription drugs, such as Xanax—made with pill presses shipped from China. See “Buyer Beware Drugs” for more information on this.

In November of 2017 STAT News reported a Chinese official disputed the claim made by President Trump that most of the fentanyl coming to the US was produced in China.  He said: “the evidence isn’t sufficient to say that the majority of fentanyl or other new psychoactive substances come from China.” However, both the DEA and the White House Office of National Drug Control Policy previously pointed to China as North America’s main source for fentanyl, related drugs and the precursor chemicals used to make them. Bejing previously regulated fentanyl and 18 related compounds, including carfentanil, furanly fentanyl, acryl fentanyl and valeryl fentanyl.

Then Reuters reported in January of 2018 how a congressional report of a year-long probe by a Senate subcommittee found it was easy for buyers in the US to purchase fentanyl, often in large quantities, from China through the internet. Staff of the committee focused on six “very responsive” providers in China—out of hundreds of pages of website offering fentanyl for sale. The Chinese sellers preferred to ship the fentanyl using Express Mail Service, which operates worldwide through each country’s postal service, including the U.S. Postal Service. “Surcharges are applied, the investigators said, for customers demanding shipment through private delivery services, such as FedEx, DHL and United Parcel Service, because of the greater likelihood the goods would be seized.”

A Chinese foreign ministry spokesperson said she was unaware of the specifics, but that anti-drug coordination was one of the highlights of China-US law enforcement cooperation. “We stand ready to work with the US to enhance our coordination in this field.” The investigators found that the US Postal Service only received the electronic data of just over one-third of all international packages, “making more than 300 million packages in 2017 much harder to screen.” A spokesperson said the Postal Service continues to work to address this issue. Implementing the use of electronic data was slowed by the need to negotiate with international partners.

The Canadian province of Prince Edward Island is slightly larger than the state of Delaware and the only subnational jurisdiction in North America with no mainland territory. Farming is the heart of the province’s economy, which produces 25% of Canada’s potatoes. It consists of the main island (Prince Edward Island) and 231 minor islands. With only around 143,000 residents, it would seem to be one of the last places in North America to be impacted by the fentanyl crisis. But that’s not true any more. In the beginning of May in 2018, the province’s Department of Health reported fentanyl was found in cocaine seized by police in Charlottetown, the capital city of the province.

About the same time Vox reported on the sharp increase of cocaine and fentanyl overdose deaths in the US. Using data from the CDC, Vox found the number of overdose deaths from cocaine and synthetic opioids to be 4,184, 17 times greater than the 245 deaths reported in 2013. Keith Humphreys, from Stanford University, said no one knows for sure what’s going on. “I can tell you my guesses, but I’m pretty sure no one really, honestly knows what’s going on.” Mixing cocaine and fentanyl in a speedball is possible, but the presence of both drugs in a post mortem toxicology report does not mean they were used at the same time. This is the simplest and most plausible explanation, but it wouldn’t apply to the Charlottetown seizure on Prince Edward Island.

A dealer accidentally mixing cocaine and fentanyl, while possible, is even more unlikely. It would have to be a drug operation that buys and sells both cocaine and opioids. Then the individuals cutting the product would have to neglect to clean the space used for cutting the drugs before switching from one drug to the other. But the picture of dumb and dumber drug dealers who just don’t realize what they are doing doesn’t “cut” it.

A third possibility is that dealers or the traffickers above them are purposely mixing cocaine and fentanyl. “With or without the buyer’s knowledge, drug sellers or someone up the chain may be mixing cocaine and fentanyl before the product hits the street.” Two possible reasons would be to give a supposed cocaine product an extra kick; or to get cocaine users hooked on opioids. Experts are skeptical this practice is widespread. Cocaine and fentanyl have opposite drug effects, “which can be unpleasant to someone who wants a pure upper or downer experience.” One expert said the dealer was already making money off the person. “Why would you want to kill them or piss them off?” Yet while this explanation is unlikely and highly speculative, it seems the best explanation for the Charlottetown seizure.

Although what follows is purely speculative, I’d suggest someone intentionally mixed cocaine and fentanyl as an experiment to see if the newer, “edgier” cocaine had a market; it didn’t. Reluctant to waste the drug batch, the trafficker sold it down the supply chain to dealers in Prince Edward Island. If the price was low enough, it may have been that the local dealers didn’t ask too many questions.

Whatever the true explanation is, individuals using illicit drugs today have stepped through the looking glass into a brave new world where what you get may not be what you thought it was.