Polysubstance Misuse-Next Overdose Crisis Materials

IT IS NO LONGER JUST AN OPIOID PROBLEM: POLYSUBSTANCE MISUSE AND THE FOURTH WAVE OF THE OVERDOSE CRISIS

GERALD GIANUTSOS, PhD, JD

Gerald Gianutsos, Ph.D., J.D., is an Emeritus Associate Professor of Pharmacology at the University of Connecticut School of Pharmacy.

Topic Overview

The drug overdose crisis in the United States began in the 1990s. This crisis was fueled by a growth in opioid prescriptions by healthcare providers and is referred to as the “first wave.” The first wave was followed by a second wave, driven by a rise in heroin use. A third wave followed, which was highlighted by the use of synthetic opioids. Now, a fourth wave has emerged in the opioid overdose crisis. This wave is marked by polysubstance misuse involving the use of fentanyl combined with stimulants. These waves have caused a progressively higher number of drug overdose deaths in the United States. This activity reviews the distinctive features of each wave of the drug overdose crisis and the increasing role of polysubstance misuse in the fourth wave. It also discusses the successes and failures of regulatory and public policy decisions that have been applied to combating this drug overdose crisis and the dangers and risks of stimulant misuse.

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Pharmacy Technician  0669-0000-24-118-H08-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation

Release Date: August 15, 2024 Expiration Date: August 15, 2027

Target Audience: This educational activity is for pharmacists and pharmacy technicians

How to Earn Credit: From August 15, 2024, through August 15, 2027, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “Educational Activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Describe the evolution of the opioid and drug overdose crisis.

Review how polydrug misuse has become the dominant factor in overdose deaths.

Discuss the characteristics and risks of stimulant misuse.

Characterize how regulatory and public policy decisions have been applied to combating drug overdose.

Disclosures

The following individuals were involved in developing this activity: Gerald Gianutsos, PhD, JD, and Pamela Sardo, PharmD, BS. Pamela Sardo and Gerald Gianutsos have no conflicts of interest or financial relationships regarding the subject matter. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.

© RxCe.com LLC 2024: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity

It Is No Longer Just an Opioid Problem: Polysubstance Misuse and the Fourth Wave of the Overdose Crisis

Introduction

The drug overdose crisis in the United States began in the 1990s. This crisis was fueled by a growth in opioid prescriptions by healthcare providers and is referred to as the “first wave.” Efforts to address this crisis have failed to reduce misuse and death from drug overdose. Instead, a second wave, driven by a rise in heroin use, and a third wave, which was highlighted by the use of synthetic opioids, followed. A fourth wave has emerged in the opioid overdose crisis. This wave is marked by polysubstance misuse involving the use of fentanyl combined with stimulants. These waves have caused a progressively higher number of drug overdose deaths in the United States. This activity reviews the distinctive features of each wave of the drug overdose crisis and the increasing role of polysubstance misuse in the fourth wave. It also discusses the successes and failures of regulatory and public policy decisions that have been applied to combating this drug overdose crisis and the dangers and risks of stimulant misuse.

Prevalence of Drug Overdose

Deaths due to drug overdose continue to be a major public health problem.1 The frequency of overdose fatalities has maintained a steady increase over the past three decades, with a slight decline reported from September 2023 forward.1

Since 2019, drug overdose deaths have become the number one cause of accidental deaths in the U.S., surpassing casualties resulting from motor vehicle accidents.2 The overwhelming majority of drug overdose deaths result from an overdose of an opioid. In 2020, approximately 3 out of 4 overdose deaths involved opioids,3 compared with an opioid-related death rate of 50% in 1999.4

In the twelve months ending August 2023, the number of overdose deaths rose to a new record of more than 111,000 reported in June 2023.1 By comparison, 16,849 deaths were reported in 1999. This represents more than a 6-fold increase by 2023.5

Drug overdose deaths are usually due to the misuse of opioids. In 2021, almost 70% of deaths were due to overdose from illegally manufactured fentanyl (IMF).6 However, the current “fourth wave” of overdose deaths is increasingly characterized by polysubstance misuse, especially with stimulants combined with fentanyl.7,8

In the U.S., recent data indicate that drug overdose deaths involving a combination of fentanyl and stimulants have increased 50-fold since 2010.8 These fatalities accounted for 32% of lethal U.S., overdoses in 2021.8 Polysubstance use may result from intentional, simultaneous use of multiple substances or the unintentional use of a drug sample that has been contaminated with another substance. Available data does not differentiate between the two circumstances, but evidence points to intentional co-use as the dominant factor.8

The First Three Waves of the Drug Overdose Crisis

The modern overdose crisis has occurred in four waves, with different substances playing a predominant role. The first three waves, discussed in this section, were marked by distinctive trends in drug use: the first wave was driven by prescription opioids, the second wave by an increase in heroin use, and the third wave by synthetic opioids, such as fentanyl.

The First Wave: Prescription Opioids

Emphasis on Pain Management

The first wave began in 1996 and was largely due to overdose from prescription opioids, fueled by a greater emphasis on treating chronic pain.9 Healthcare providers in the 1990s began prescribing increasing amounts of

opioid analgesics to address what was perceived at the time to be a widespread problem of undertreated pain.10 Many healthcare advocates and professional organizations supported new standards in the way that pain is acknowledged and managed, including characterizing pain as the “Fifth Vital Sign.”11

In 2000, Congress proclaimed the upcoming decade as the "Decade of Pain Control and Research” as part of the Pain Relief Promotion Act.12 In the act, Congress acknowledged that inadequate pain management for malignant and nonmalignant diseases was a “serious public health problem” and that “in the first decade of the millennium, there should be a new emphasis on pain management and palliative care.”12

The Pain Relief Promotion Act amended the Controlled Substances Act (CSA) to support the concept that alleviating pain or discomfort in the usual course of professional practice is a legitimate medical justification for the dispensing, distributing, or administering of a controlled substance, even if it may increase the risk of overdose.12

In addition, The Drug Enforcement Administration (DEA) amended its rules for prescribing controlled substances in 2007 to allow prescribers to issue multiple prescriptions for a Schedule II controlled substance at a single office visit.12

These policy changes led to substantial increases in opioid prescriptions and resulted in more dependence among patients, greater diversion to non- medical uses, and skyrocketing increases in overdose deaths.13

Efforts to Mitigate the First Wave Opioid Crisis

In response to the developing overdose crisis, opioid prescribing was discouraged, and other steps were taken to deter misuse and diversion.13,14 Efforts to mitigate misuse and diversion included the implementation of prescription drug monitoring programs (PDMP), increasing physician awareness of the appropriate use of opioids along with new prescribing

guidelines, legislation to limit the proliferation of pill-mills, and development of misuse-deterrent opioid formulations.14-16 The Centers for Disease Control and Prevention (CDC) established guidelines to help curb the overdose crisis from opioid prescribing.16 The CDC’s guidelines were not universally well- received. The AMA stated that patients needing pain relief were being harmed by “arbitrary restrictions on opioid therapy” recommended by the CDC’s 2016 guidelines.17

These measures were largely successful in reducing opioid prescriptions. The national opioid dispensing rate declined from 2010 to 2015.13 However, from 2010 through 2012, the average duration of an opioid prescription increased to >30 days. The rate of these longer prescriptions stabilized, followed by a substantial decrease in shorter prescriptions (<30 days) after 2012.13 The CDC interpreted this to mean that fewer patients were started on opioids to treat pain after 2012. However, patients already receiving opioids were more likely to continue receiving them.13

The Second Wave: Heroin

The efforts to reduce opioid prescriptions that gave rise to the first wave did see a significant decline in opioid prescriptions, and by 2020, the dispensing rate had fallen to its lowest level in 15 years.14 However, despite these mitigation efforts, total opioid overdose death rates continued to soar, leading to the Second Wave.9,14,15

The second wave began around 2010.9 As prescription opioids became harder to obtain, users turned to other means of obtaining opioids. Some shifted to non-prescription opioids, primarily heroin.9,14 During this period, the heroin supply expanded, and its price dropped, making it more available to users.9,14

The Third Wave: Synthetic Opioids

The third wave started in 2013 and was associated with an increased supply of illicitly manufactured and smuggled synthetic opioids, especially

fentanyl and its analogs.9,18 Fentanyl is a powerful mu-opioid receptor agonist that is 75–100 times more potent than morphine.19 Fentanyl was originally introduced more than 50 years ago as an alternative to morphine as an analgesic and anesthetic for surgical use due to its rapid onset, short duration of action, high potency, and limited cardiovascular risks compared to morphine.19 The potential for fentanyl misuse was initially believed to be minimal, but it has emerged as a dangerous recreational substance.19 Although commonly described in the media as a recent phenomenon, fentanyl has been a factor in illicit drug overdose for decades, having been used as an adulterant in street drug supplies since at least 1979.20

The unprecedented growth in overdoses due to fentanyl was driven by users either intentionally seeking the higher potency opioid as their drug of choice or unknowingly using fentanyl, which was added to their preferred drug, most commonly heroin, to improve its rewarding properties and lower production costs.14,18 The current rise in fentanyl is considered to be more a supply rather than a demand-driven event, replacing heroin during a heroin shortage.21 The flow of fentanyl into the U.S., has increased since its rise to prominence in 2014, with newer source countries and transit points emerging in the global supply chain.22 The primary source countries for fentanyl trafficking are China and Mexico, with India also emerging as an important source of precursor chemicals and finished fentanyl powder.22 Other factors that have contributed to the increased use of fentanyl include more efficient methods of synthesis and lax or ineffective regulatory environments in source countries18,21 Users are also subject to greater risks by the concealment of synthetic opioids in powders sold as heroin or pressed into counterfeit pills.18

The COVID-19 pandemic worsened matters as social isolation, loss of economic opportunity, boredom, despair, disruption of normal routines, and political polarization increased distress. At the same time, the lockdowns made it more difficult to access treatments, resources, and emergency services that help people suffering from opioid use disorder (OUD).23,24 Lockdowns and distancing efforts also made it less likely that an individual who overdoses would be discovered and given naloxone in time to prevent lasting injury or death.24 The decreased access to interventions and treatment led some

patients to seek new remedies independently, often from unknown, less reliable sellers supplying contaminated products.23

In addition, COVID-19 mobility restrictions made it more challenging to smuggle illegal drugs into the country, and border restrictions made it harder to move bulkier drugs.25 As a result, smugglers increased their reliance on fentanyl, which, due to its potency, can be transported in small quantities and is easier to traffic by mail.20,25 This helped make fentanyl more available to areas in the U.S., that had not previously been as impacted by the drug.25 Before the pandemic, fentanyl mainly affected urban areas in the Eastern regions of the U.S., where it could be easily mixed with the powdered heroin popular in this region.25

Alarmingly, overdose deaths have not fallen with the end of the pandemic as may have been expected.8 Factors contributing to the sustained dangers from fentanyl include an expansion in the black-market production and supply of counterfeit prescription drugs containing fentanyl and the increase in concurrent use of other illicit substances.8

In some areas, fentanyl and its analogs have virtually displaced traditional opioids.18 They have become the leading cause of drug overdose deaths, accounting for almost 2/3 of overdose deaths in 2021.18,20

The Fourth Wave: Polysubstance Misuse

More recently, the drug overdose crisis has transitioned again and has become more frequently associated with the simultaneous use of multiple substances. Multi-substance use has been dubbed the “fourth wave.”26 Although many individuals prefer using a specific drug or drug class, the use of multiple substances is common.14

In particular, there has been a surge in the simultaneous use of psychostimulants with opioids; more than half of reported psychostimulant overdose deaths in 2019 also involved an opioid.27 Studies have shown that there is an overlap between the use of opioids and other substances and that

OUD frequently coincides with other substance use disorders.28 One study looking at a nationally representative U.S., database found that almost 60% of individuals with OUD were polydrug users, and over 25% had at least two other substance use disorders along with OUD.29

The surge in overdose deaths has most commonly been observed in individuals using fentanyl with CNS stimulants.7,18 The combination of an opioid with cocaine has long historical roots, traditionally being referred to colloquially as a “speedball.”26 However, the concurrent use of opioids and stimulants has risen markedly, and overdose deaths from the simultaneous use of both agents have been rising since 2015.27 In addition to stimulants, fentanyl combined with benzodiazepines or the veterinary sedative, xylazine (“tranq”), have also driven the trend towards dangerous polysubstance use.8

There are many reasons why drug users may combine other substances with opioids: one drug may enhance the reward/high produced by the other, or a drug may block or reduce the undesirable effects of the other.27 The use of multiple drugs may also be an attractive alternative during periods of scarcity of a user’s preferred agent.30

In the case of opioids and psychostimulants, it has been suggested that combined use may establish an equilibrium between the activation produced by the stimulant and the sedation produced by opioids to balance out their effects and allow the user to maintain near-normal functioning. Alternatively, the use of both drugs may produce a high with two entirely different alternating pleasurable sensations.14 However, in addition to the increased risk to an individual by the consumption of two different drugs with a potentially unpredictable pharmacological interaction, there is also the risk of creating the “illusion” that the drugs are masking or preventing toxicity, misleading the user to use more of the drug and increasing the risk of overdose.31

Studies show that there is an increase in the use of methamphetamine in individuals with OUD.30 This observation is consistent with epidemiologic data showing that there was a 50-fold increase in the methamphetamine

mortality rate between 2010-2021; 61% of methamphetamine-associated deaths included fentanyl in 2021.32 Similarly, the rate of drug overdose deaths involving both cocaine and opioids increased nearly 5.5-fold from 2009 to 2019.27 By 2019, three-quarters of the 15,883 drug overdose deaths involving cocaine also involved one or more opioid.27 In all, fentanyl and stimulants accounted for the largest proportion of overdose deaths in 2021; overdoses in which either fentanyl or a stimulant is involved rose to 84% in 2021 compared with 23% in 2010.7,27

The risk of fatality is greater when stimulants are combined with opioids than when stimulants are used alone.32 Between 2013 and 2019, the rate of drug overdose death increased at a faster rate when both cocaine and opioids were involved compared with cocaine alone.27 From 2009 through 2016, the rate of overdose deaths involving psychostimulants without opioids was higher than the rate involving psychostimulants with opioids. However, this pattern reversed between 2017 and 2019, with higher rates of overdose deaths when both psychostimulants and opioids were involved.27

These drug combinations also follow a geographic pattern, with the Northeast region of the U.S., being affected first by an increase in the co-use of stimulants with heroin.7,27 By 2021, all the states in the Northeast had a stimulant as the most common substance co-involved with an opioid; cocaine was the most commonly co-involved substance in seven states and methamphetamine in two.7 While the highest percentage of opioid-stimulant fatalities was in the Northeast, the West, traditionally a hotbed for stimulant misuse, was the lowest.7

Prevalence, Risks, and Legal Considerations of Stimulant Misuse

The focus of this activity has been on the simultaneous use of opioids and psychostimulants. Still, the CDC reports that drug overdose deaths involving psychostimulants have been increasing even without the involvement of an opioid.33 Rates of overdose deaths from psychostimulants have been increasing since 2010. Nearly 33,000 Americans died from an overdose involving psychostimulants with misuse potential in 2021, which was

a 37% increase from the previous year.33 Deaths in the U.S., from psychostimulants with misuse potential (largely methamphetamine) reached almost 33,000 in 2021 and 34,000 in 2022.33,34 This was a 37% increase over 2020 and compares with only 547 in 1999 and fewer than 6000 as recently as 2016.33,34 Drug overdose deaths from all stimulants rose more than four-fold from 12,122 in 2015 to 53,495 in 2021.35

The emerging risk of stimulant misuse and overdose resembles the earlier opioid epidemic since it involves the use of illicit products, largely methamphetamine, and cocaine, as well as the non-medical use of prescription medications.36 Pharmacists should note that it is estimated that 5 million Americans (just under 2% of the population) misused prescription stimulants in 2020.33

The most common stimulants with high misuse potential are methamphetamine and cocaine. Methamphetamine can be injected, smoked, snorted, or taken by injection.37 The initial methamphetamine “rush” is characterized by increased energy and alertness, an elevated positive mood state, and decreased appetite.37 Methamphetamine has a relatively long half- life among psychostimulants (for example, in comparison to cocaine and nicotine), ranging from 8 to 12 hours.37

The U.S., has previously witnessed epidemics of stimulant misuse and overdose in its history.36 An early example occurred in the 1930s when amphetamine marketed as an OTC inhaler (Benzedrine) became popular and also became a common treatment for depression.38 In the 1980s, it was dubbed “America’s Most Dangerous Drug.”39

Stimulant Misuse Risks

Psychostimulants can affect many organs in the body. Stimulant-related deaths are usually due to severe alterations in cardiovascular and cerebrovascular function.40 Autopsy studies of methamphetamine users have detected increased frequencies of accelerated coronary artery disease and cardiac hypertrophy.37 Cardiovascular events commonly seen in cocaine users

include sudden cardiac death, myocardial infarction, cerebrovascular infarction, cardiac arrhythmia, hypertension, EKG abnormalities, and acute rupture of the aorta.37,40,41 These can occur even in young users.37 A study noted subarachnoid hemorrhage occurring within minutes after intranasal insufflation of cocaine.41 Cocaine affects multiple other organ systems involved with neurologic, psychiatric, obstetric, pulmonary, dermatologic, and gastrointestinal function.41 Cocaine is known to induce convulsions either by directly affecting neurons or indirectly by inducing hyperpyrexia; the hyperpyrexia can also be fatal.41

Like opioid toxicity, the acute effects of stimulants can lead to death in first-time users. However, stimulant toxicity is often an outcome of long-term cumulative exposure.40,42 Long-term use of stimulants can induce adverse chronic conditions such as cardiac structural disruption (e.g., cardiomyopathy) and electrical conduction disorders, which can contribute to cardiovascular and cerebrovascular events.40,42 Individuals who have died as a result of acute stimulant toxicity often have higher rates of pre-existing cardiovascular disease than those who die from opioid overdose or injuries.41 People using cocaine frequently have undiagnosed, progressive cardiovascular disease, and many remain undiagnosed until they arrive at an emergency department with an acute event. A study of women with unstable housing found that those who co-used cocaine and alcohol had higher levels of cardiac injury even after adjusting for other risk factors.42

Although stimulant users can die as a direct result of an acute overdose, chronic physical and mental deterioration is likely to produce long-term effects affecting the user’s health long after exposure to the drug.43 Unlike opioids, which have relatively less risk of long-term health impacts to users who do not overdose, people with methamphetamine use disorder are more likely to die from the chronic physical and mental diseases related to their meth use than they are to die from an acute meth overdose.43 In addition to cardiovascular and CNS disruption, chronic methamphetamine use can cause renal failure, and the suppression of appetite can cause malnutrition and vitamin deficiency.43 The mental disruption associated with chronic methamphetamine use can also lead to difficulties in managing chronic

medical conditions, and users are more likely to take risks leading to injury or sexually transmitted diseases or other infectious illnesses.43

Consequently, many users who die from health problems caused by methamphetamine use disorder (MUD) do not show up in overdose mortality data, so focusing on overdose statistics may underestimate the effect of stimulants on mortality.43

Legal Considerations

During earlier instances of rampant stimulant misuse, policymakers enacted various measures intended to curb the availability of drugs and limit misuse. In the early 2000s, many states passed laws restricting the sale of methamphetamine precursors found in OTC decongestant products.37

Pharmacists are familiar with the federal Combat Methamphetamine Epidemic Act (CMEA) passed in 2005.44 The act regulated the OTC retail sales of ephedrine and pseudoephedrine, which are precursor chemicals for clandestine production of methamphetamine. The CMEA requires verification of all purchasers, record keeping, limits on daily and 30-day purchase amounts, and required that products be stored behind the counter or in a locked cabinet. It also requires purchasers to show a valid, government-issued photo ID and to sign a logbook.

These measures produced a significant decrease in the availability of methamphetamine in many parts of the U.S., as indicated by a decrease in the number of meth lab seizures by law enforcement and decreased emergency room visits and treatment admissions associated with methamphetamine.37,43 Seizures peaked in 2004, and by 2018, most seizures were from very small operations.43 As noted above, today, most methamphetamine is imported from Mexico, where suppliers use different precursors, and the product is more potent, of higher purity, and less expensive.43

The crack cocaine epidemic arose in the 1980s. The crack cocaine epidemic generated more onerous and controversial proposals.45 The Crack scare began in 1986, and societal fear was fueled by exaggerated media coverage and congressional willingness to pass anti-drug laws that promoted the War on Drugs.45

The perceived greater dangers associated with this new form of cocaine prompted responses that more closely prioritized law enforcement rather than public health policies, and the result was disproportionate consequences for Black communities.36 The Anti-Drug Abuse Act, passed in 1986, had several components aimed at curbing the distribution of illicit drugs.46 The act amended the Controlled Substances Act to provide that controlled substance analogs (“designer drugs”), including many synthetic stimulants, would be treated as Schedule I substances and banned the operation of locations intended for the use of illegal drugs. (The latter provision was known as the "Crackhouse Law" and was amended by the RAVE Act in 2003.) The most controversial aspect of the new law, aligned with the Comprehensive Crime Control Act of 1984, substantially increased the number of drug offenses carrying mandatory minimum sentences.47

Among other provisions of the law, Congress distinguished powder and free-base (“crack”) cocaine and set a differential requiring lesser quantities of crack to trigger mandatory five- and ten-year penalties.47 The differential set was 100:1, as such, a five-year sentence would be imposed for trafficking in 500 grams or more of powder cocaine, but only 5 grams of crack would trigger the same penalty.

Lawmakers argued that it was imperative that the proposal immediately be passed, citing the intense addictive properties of the drug and the epidemic of crack cocaine use among youth.48 Congress offered five justifications for the 100:1 ratio. These justifications were based on the assumptions that the crack formulation is more highly addictive than the powdered form of cocaine; crack use is connected to violent crime; there is a large prevalence of crack use among youth; there is a serious in-utero threat to children borne by

pregnant users; and the low cost of crack relative to powder cocaine made it more readily available and more likely to be consumed in large quantities.47,48

This resulted in street-level crack dealers being punished, equivalent to a wholesale/importer dealer in powdered cocaine.47 The one-hundred-to-one ratio adversely affected African Americans because African Americans disproportionately consume crack cocaine compared with Caucasians who preferred the powder form, and its relatively low cost made crack cocaine much more prevalent in inner cities.46,48

In 1995, the U.S., Sentencing Commission concluded that the racial disparity created a "racial imbalance in federal prisons and led to more severe sentences for low-level crack dealers than for wholesale suppliers of powder cocaine."47 Later, the Commission determined that the ratio was created based on a misconception of the dangers of crack cocaine, and the ratio was reduced to 18:1.

Congress again turned its attention to stimulants in 2022 by enacting the Methamphetamine Response Act, which declared methamphetamine as an emerging drug threat and directed the Office of National Drug Control Policy to implement a methamphetamine response plan.49 Among the recommendations were efforts to reduce trafficking and production, continuing federal oversight of pill press and tableting equipment importation, sales, and illicit use, and research support to further understand the correlation between cessation of methamphetamine use and the reversibility of short and long- term negative health and social effects.49 In October 2023, the FDA issued new industry guidance to encourage the development of new treatments for stimulant use disorder.50

The Pharmacy Team’s Role in Combatting the Overdose Crisis

Pharmacy professionals are part of a broader healthcare team and are primarily responsible for dispensing drugs. They can and should play a pivotal role in helping to prevent the diversion of prescription drugs. This can be done by addressing drug misuse with other healthcare professionals on the team

and educating patients about the proper storage and disposal of their medications. Pharmacy teams can educate the community regarding overdose-reversing drugs as a key part of the HHS Opioid Strategy.51

Additional Resources

Summary and Key Points

Drug overdose deaths in the United States now surpass 100,000 annually. The crisis, mostly due to overdose of opioids, has passed through three previous waves: Prescription drugs, heroin, and illicitly manufactured fentanyl. The most recent wave is largely due to polysubstance misuse, typically opioids mixed with psychostimulants or other depressant drugs.

Deaths involving combinations of fentanyl and stimulants have increased. Simultaneously abusing multiple substances introduces additional dangers for the user. Psychostimulants convey significant cardiovascular risks not normally associated with opioid toxicity.

Individuals consuming multiple substances are at increased risk of overdose, and the non-opioid substances being mixed with fentanyl are not responsive to naloxone, the opioid overdose rescue agent. Patients with a verified overdose of co-administered opioids and stimulants had significantly higher total naloxone requirements for reversal than patients overdosing on opioids alone.

There are important differences between opioid and stimulant use disorders. The concern with opioids is primarily the dangers of death from acute overdose, and the corresponding treatment approach is overdose reversal and promoting abstinence. The stimulants, on the other hand, are more likely to produce long-term health consequences related to cardiovascular and neurological damage, and the physical and mental impacts can persist even during abstinence. This necessitates a different approach to treatment and services. In summary, healthcare providers should appreciate that the factors behind the rise in drug overdose deaths continue to be a moving target. Pharmacists may be effective members of a healthcare team by staying abreast of current and future therapies for stimulant use disorder.

Course Test

The current overdose crisis has occurred in waves. The current fourth wave refers to dangers from polysubstance misuse. What was the cause of the first wave?

Prescription opioids

Illegally manufactured fentanyl

Crack

Heroin

What percentage of individuals with opioid use disorder are polydrug users, according to recent statistics?

10

25

50

60

Overdose deaths due to the combination of fentanyl and stimulants accounted for less than 1% of total overdose fatalities in 2010. How much did this increase by 2021?

Less than 1%

25%

Doubled

50-fold

How do cocaine and methamphetamine differ significantly?

Cocaine produces fewer acute dangerous effects than methamphetamine.

There is no smokable form of methamphetamine comparable to crack.

Methamphetamine has a much longer duration of action than cocaine.

Cocaine is rarely mixed with opioids.

Stimulants produce effects on multiple organ systems. Which effect is believed to be responsible for the surge in acute stimulant overdose?

Cardiovascular irregularities

Renal failure

Drug-induced psychosis

Respiratory depression

What drug was dubbed “America’s Most Dangerous Drug” in the 1980s?

Fentanyl

Cocaine

Methamphetamine

Marijuana

What is an important public health difference between opioid and stimulant misuse?

One of the major concerns with stimulant misuse is the effect of chronic use on health rather than acute overdose.

Reversal agents are more effective in the case of stimulants than opioids.

Stimulant misuse is limited to the United States Southwest and is not a national problem like opioids.

Stimulant overdose deaths rarely occur in the absence of co- administered opioids.

Although most of the risks with stimulant misuse are due to illicit substances, pharmacists should be aware that prescription stimulants are also a contributing factor. Approximately how many people in the U.S. misused prescription stimulants in 2020?

500,000

1,000,000

5,000,000

10,000,000

Why was the Combat Methamphetamine Epidemic Act enacted?

To reduce the illegal smuggling of methamphetamine from Mexico.

To restrict the sale of OTC decongestants that are used as precursors for manufacturing methamphetamine.

To further restrict the prescribing of prescription amphetamines.

To reduce the yearly quantity of stimulants that a manufacturer could produce.

Why was the Anti-Drug Abuse Act of 1986 so controversial?

It increased the penalties for possession of illicit prescription opioids.

It differentiated between mandatory sentences for possession of powdered cocaine and crack cocaine to the detriment of black communities.

It encouraged loosening restrictions on the use of opioids to treat pain.

It sought to make all amphetamines Schedule I drugs.

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