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The Role of Primary Care and Integrated Behavioral Health in Polysubstance Use

Purpose

This page represents a brief overview of the available research on addressing polysubstance use in a primary care setting with a focus on leveraging an integrated behavioral health team. Polysubstance use is known to impact patients physically and mentally in numerous ways and is often found in primary care patients who are being treated for co-occurring mental disorder such as opioid use disorders, depression, post-traumatic stress disorder (PTSD), and others. An integrated behavioral health team in primary care can provide some of the necessary support for the primary care provider (PCP) and patient to begin addressing this complex issue, as well as coordinate care with often needed specialty substance use disorder (SUD) services.

Definition

Polysubstance use is the use of more than one substance of misuse. Use of multiple substances can be at the same time or sequential, or at separate times. Polysubstance includes a spectrum of severity from concurrent use of multiple substances to having multiple substance use disorders. And while polysubstance use is often intentional, it can also be unintentional, such as when a drug is mixed or cut with another drug without the person's knowledge. The phrase "polysubstance abuse" is sometimes referenced, but it is recommended to avoid this phrase to reduce stigma and negative bias.

People intentionally use multiple drugs for several reasons that may include:

  1. Modify or enhance the effects of a single substance
  2. Compensate for the effects of one substance by taking another
  3. Prevent withdrawal symptoms
  4. Cope with daily effects of trauma, life circumstances, or other health problems
  5. Unavailability of their primary drug of choice1
  6. Coerced to use additional substances by abuser

Table of Contents

This page covers the following topics.

  1. Why is Polysubstance Use Important for Primary Care providers to Understand and Address?
    1. Polysubstance Use is Common
    2. Polysubstance Use Places Patients at Risk for Worse Outcomes
    3. Primary Care is in an Optimal Position to Start to Address Polysubstance Use
  2. What Should Primary Care Practices Do to Address Polysubstance Use?
    1. Look for all Types of Substance Use
      1. Initial Screening
      2. Ongoing Monitoring of Substance Use
    2. Educate Patients on the Risks of Polysubstance Use
    3. Continue Treatment of their Known Substance Use Problem
      1. Smoking Cessation – Impact on Other Substance Use
    4. Offer Concurrent Substance Use Treatment
      1. Withdrawal Management Considerations in Polysubstance Use
      2. Offer Medications, as Appropriate, for all Substance Use Disorders
      3. Medications for Multiple Substances
      4. Offer Psychosocial Support for Polysubstance Use, if Available
      5. Leverage Digital Therapeutics Where Possible
    5. Screen and Treat Co-Occurring Mental Health Problems
      1. Screen and Diagnose Mental Health Disorders in the Context of Polysubstance Use
      2. Assess for Suicidal Ideations at the Beginning of Engagement and Throughout Treatment
  3. Final Considerations for Incorporating Polysubstance Use Treatment into Integrated Behavioral Healthcare Models
  4. Resources for Providing Care for Patients with Polysubstance Use
  5. Explore More on the Academy Portal
  6. References

Polysubstance use is common

According to the National Survey On Drug Use and Health from 2019, people who use one substance often use another.2

[NOTE: Cannabis/Marijuana: the DSM term is "Cannabis Use Disorder". That said, these terms are often used interchangeably. Throughout this document, we have chosen to use the term as it appears in the reference being cited.]

Concurrent Substance Use

Substance

Marijuana

Opioid

Cocaine

Methamphetamine

Alcohol

Heavy Alcohol Use

45%

9.2%

11%

1.7%

Not Applicable

Heavy Marijuana Use

Not Applicable

16%

16.3%

3.3%

16.2%

Opioid

53%

Not Applicable

15.6%

8.7%

14.7%

Methamphetamine

68.1%

43.7%

32.2%

Not Applicable

13.4%

Source: The National Survey on Drug Use and Health: 2019 – Presentation

In addition, many individuals with one substance use disorder are at risk of having a concurrent substance use disorder.3 Among people with a cocaine use disorder, nearly 60% have a co-occurring alcohol use disorder and over 20% have a marijuana use disorder,4 and among people with an opioid use disorder, more than 25% have at least two other substance use disorders.5

Finally, people with mental health disorders have been found to have higher rates of substance use and substance use disorders versus the general population. Having a mental disorder can increase the risk for developing multiple substance use disorders.

Polysubstance use places patients at risk for worse outcomes

When compared to people with a single SUD, polysubstance use is associated with higher rates of:

  • Lifetime suicide attempts, arrests, and incarceration6
  • Financial and legal problems6
  • More severe medical and psychiatric comorbidities (e.g., the prevalence of a mental disorder is higher among those who are dependent on multiple psychoactive substances, such as heroin, alcohol, or cocaine, than those who use one substance)7
  • Greater difficulty adhering to substance use disorder treatment8, 9
  • Increased likelihood of overdose10, 11

Primary care is in an optimal position to start to address polysubstance use

  • The majority of patients with substance use disorders do not seek or do not have access to specialty substance use treatment, but are overrepresented in primary care.14
  • The majority of opioid use disorder (OUD) treatment is provided by PCPs.15
  • Substance use, mental disorders, and other general medical conditions are often interconnected.14
  • Integrated care has the potential to reduce health disparities.14
  • Delivering substance use disorder services in mainstream health care can be cost-effective and may reduce intake/treatment wait times at substance use disorder treatment facilities.
  • Integration can lead to improved health outcomes through better care coordination.14

Addressing polysubstance use in primary care can be done. This section explores the various components of doing this, from screening for multiple substance use and mental health disorders, to treatment options, and the use of team-based care. While most clinics will not be able to apply all of these recommendations, clinics can pick and choose which elements could be adapted in an effort to better meet this need.

Look for all types of substance use

Initial Screening

Identifying polysubstance use can take many forms. Incorporating universal yearly drug and alcohol screening, as recommended by the U.S, Preventative Services Task Force (USPSTF),16, 17 is a good way to avoid missing people as well as to reduce the impact of provider bias. The Alcohol Use Disorders Identification Test (AUDIT)18 or AUDIT-C,19 a shorter version of the 10-item AUDIT, are good screeners to look for the spectrum of risky drinking through an alcohol use disorder. There are several drug screeners that primary care settings can consider that include the Single Item Screener, the DAST-10, and the Tobacco, Alcohol, Prescription medication and other Substance Use (TAPS).20

Screening Tools for Drug and Alcohol Use

Tool

Alcohol

Drugs

Self-administered

Clinician-administered

Validated in PC

AUDIT-C
4 question version of full AUDIT

X

Not Applicable

X

X

X

AUDIT

X

Not Applicable

X

X

X

Drug Single-Item Screener
-may miss legal cannabis due to wording of the question. Consider asking about cannabis separately

X

X

X

X

X

TAPS

X

X

X

X

X

Source: Common Data Elements – Instruments

Additional resources on screening for drug and alcohol use can be found in The Academy's Substance Use Tools & Resources.

For patients who are already being treated for a single substance use disorders, polysubstance use can also be assessed through the recommended routine urine drug screening tests.21 However, drug testing only detects recent drug use and may not be able to detect newer synthetic drugs. False positives for drug use tests are also a problem and require confirmation with gas chromatography-mass spectrometry. Talking with your laboratory to understand the limits of the different drug tests and how to order confirmatory testing is useful when there is a discrepancy between the patient's self-report and what the results say.

Ongoing Monitoring of Substance Use

In addition to initial screening for drug and alcohol use, ongoing monitoring of drug and alcohol use is recommended when people are in treatment for substance use and other mental health disorders. This can be accomplished in two ways, self-report, and drug testing.

Self-report: asking about any drug or alcohol use since the last visit is a quick way of tracking a person's substance use. This works best when a non-judgmental and empathic clinical relationship has been established from the beginning. Self-report of substance use will be most accurate when patients believe they will not suffer consequences because of their use.22 This includes reassuring patients that reported drug use will not impact their access to medications for OUD. Parents are often concerned about involvement of child protective services (CPS), and it is important to continuously address those concerns as well. CPS involvement and regulations vary across states and localities, and need to be addressed accordingly. Self-report can be one of the few ways to identify use of newer synthetic or designer drugs as laboratory testing may not include these substances in their panels or know to look for them in confirmation testing.

Substance testing:21 substance testing from a biological specimen (urine, blood, saliva, etc.) is recommended for patients in substance use disorder treatment and is not regularly done for patients in other mental health treatment. Drug testing has several limitations as noted above, but it can be a useful tool to supplement self-report. Drug testing should be used as a tool to support ongoing treatment adjustments as needed and not as a way to exact punishment. Frequency of testing can vary based on patient acuity and level of care.21

Educate patients on the risks of polysubstance use

Per the Centers for Disease Control and Prevention (CDC),23 mixing drugs is never safe because the effects from combining drugs may be stronger and more unpredictable, even deadly, than one drug alone. Furthermore, the interactions between substances carry their own harms. Patients should be counseled on these risks and there should be ongoing monitoring for substance use.

Analysis of Potential Adverse Effects of Combining Substances

Combining Substances

Potential Adverse Effects of the Combination

Stimulants with Stimulants
(e.g. cocaine and 3,4-methylenedioxy-methamphetamine (MDMA), a synthetic drug also known as Ecstasy/Molly)

  • Serotonin syndrome
  • Psychosis
  • Anxiety or panic attacks
  • Cardiovascular problems, including heart attacks, potentially fatal ones

Depressants with Depressants
(e.g. opioids and benzodiazepines)

  • Accidents or injury due to sedation (e.g. falls and car accidents)
  • Fatal overdose
  • Nonfatal overdose, which can result in permanent brain damage

Stimulants with Depressants
(e.g. amphetamines and alcohol)

  • Cardiovascular problems and heart failure
  • Respiratory infections and bronchitis
  • Dehydration, overheating, and kidney failure

Source: Polydrug Use: Factsheet

Harm-reduction strategies for the different substances being used is recommended and can include the following:

  • Not sharing drug paraphernalia, including syringes, snorting, and smoking supplies.
  • Having multiple doses of Naloxone/Narcan onsite and at the ready.
  • Do not use alone.
  • Recommend use of Fentanyl Test Strips24 to look for fentanyl in all drug products.

Additional resources to consider using include these safer use tips.25

Alcohol26

Stimulants27

Depressants28

Continue treatment of their known substance use problem

If your patent who is being treated for one substance is found to be using a second substance, it is more important to continue treatment. Continuing to treat someone's opioid use disorder has been found to help address other substance use. In one study ongoing Buprenorphine-Naloxone treatment helped reduce concurrent methamphetamine use at the same time.9 In another study, engagement in OUD treatment with Buprenorphine-Naloxone resulted in fewer days of alcohol use and cocaine use.29

Smoking Cessation - impact on other substance use

There is also a large and growing body of evidence that quitting smoking increases the likelihood of recovery from other substance use disorders.

  • Continued smoking is associated with greater odds of SUD relapse.30
  • Smoking cessation during the first year after beginning substance use treatment was associated with increased alcohol abstinence, increased drug abstinence, and increased remission of substances over a 9-year follow-up.31
  • It has also been found to improve maintaining abstinence by 25% over 6 months of follow-up.32

Therefore, the best treatment for polysubstance use is optimizing and focusing treatment efforts on the substances we have the most effective treatments for, as opposed to focusing on substances we have less effective treatments for, like benzodiazepines and stimulants.

Offer concurrent substance use treatment

Treatment of polysubstance use is more complicated than treating a single SUD and requires additional planning and coordination that may involve outside agencies. Elements of successful treatment of polysubstance use are found below and should be considered when using existing team-based models for delivering integrated substance use disorder treatment in primary care, such as the nurse care manager model33 and the collaborative care model34 (CoCM).

Withdrawal management considerations in polysubstance use35

  • The individual's simultaneous intoxication and withdrawal from two or more substances
  • Varying timeframes for experiencing withdrawal symptoms for each substance
  • Withdrawal from one or more substances
    • Withdrawal management from multiple substances is challenging to do in the outpatient setting and may be best accomplished in an inpatient setting.

If a person needs a higher level of care, ongoing care coordination is often needed as it can be challenging for patients to connect with suitable treatment program(s).

Offer medications, as appropriate, for all substance use disorders

In general, it is recommended to offer medications for each individual substance use disorder in addition to psychosocial support. First-line medications for various substances are the same in the context of polysubstance use as they would be for single substance use disorders (e.g., Buprenorphine-Naloxone/Buprenorphine/Methadone/Extended Release Naltrexone, for Opioid Use Disorder; Naltrexone/Acamprosate/Disulfiram for Alcohol Use Disorder; and nicotine replacement/Varenicline/bupropion for Tobacco Use Disorder). Per The Department of Veterans Affairs (VA) and the Department of Defense (DoD) SUD treatment guidelines,36 there is insufficient evidence to recommend for or against pharmacotherapy for the treatment of cocaine use disorder or methamphetamine use disorder. If medications for stimulant use disorders are being considered the following should be considered.

  • Medications work best in the highly motivated patient.
  • Non-stimulant and stimulant medications for stimulant use disorders do not work as well as Buprenorphine does for OUD, so do not expect the same kind of results.
  • Psychosocial treatments such as contingency management (CM) and/or cognitive behavioral therapy (CBT) have the best evidence for treatment of stimulant use disorders and should be considered as first-line treatment options

**Use of medications despite potential interactions with a patient's concurrent substance use, such as offering Buprenorphine-Naloxone in the context of illicit benzodiazepine use is recommended due to the potential benefits outweighing the harm. This position was endorsed by the U.S. Food and Drug Administration (FDA) in 2017.37 That said, the use of Buprenorphine and benzodiazepines increases the risk for death and accidental injury, and efforts should be made to reduce and avoid this combination as much as possible.**38, 39

Medications for multiple substances

There are some medications which have evidence of effectiveness for the treatment of two different substances. However, if a patient is already doing well on a medication for one substance, they should not be switched to a different medication simply to reduce the number of medications prescribed.

  • Extended-Release Naltrexone for opioid use disorders, alcohol use disorders, and methamphetamine use disorders36, 40 (when used in combination with Bupropion.) However, if a patient is doing well on Buprenorphine-Naloxone, or prefers to use Buprenorphine-Naloxone, it is not recommended that the patient be directed to extended-release naltrexone simply to treat AUD or stimulant use disorder.
  • Disulfiram has been studied in both alcohol use disorders and cocaine use disorders.41 Although Disulfiram can be an effective medication in the highly motivated, well-supported patient with alcohol use disorder, it is not useful in patients whose goals are controlled moderate drinking or who have poor medication adherence. Disulfiram has been combined with Naltrexone in patients with both cocaine use disorder and alcohol use disorder in one trial and found to help achieve abstinence from both substances over 11 weeks.42
  • Varenicline for alcohol use disorder and nicotine use disorder.43 Varenicline is considered first line for smoking cessation, and studies have found inconsistent results on reducing alcohol consumption, although it may be more helpful in reducing alcohol use in men who smoke.43, 44

Offer psychosocial support for polysubstance use, if available

There are many different evidence-based psychosocial approaches that have been developed and tested for effectiveness in treating patient use of specific substances. Therefore, psychosocial support should be part of a treatment plan for polysubstance use. While some psychosocial therapies have been tested for certain combinations of substances, there is limited data to match specific interventions with all combinations of substances a patient might be misusing. In addition, not all interventions are going to be readily available for patients in some communities. Below is a table summarizing which interventions have been found to be effective in treating different substances. When recommending psychosocial support options to patients, these modalities should be discussed.

From National Institute on Drug Abuse (NIDA) summary of evidence-based treatments,45 showing the substances for which that treatment is effective:

Effective Evidence-Based Treatment for Various Substances

Treatment Type

Alcohol

Marijuana

Cocaine

Methamphetamines

Nicotine

Opioids

Stimulants

Opiates

Cognitive-Behavioral Therapy (CBT)

X

X

X

X

X

Not Applicable

Not Applicable

Not Applicable

Contingency Management Interventions/Motivational Incentives

X

X

Not Applicable

Not Applicable

X

X

X

Not Applicable

Community Reinforcement Approach Plus Vouchers

X

Not Applicable

X

Not Applicable

Not Applicable

X

Not Applicable

Not Applicable

Motivational Enhancement Therapy

X

X

Not Applicable

Not Applicable

X

Not Applicable

Not Applicable

Not Applicable

The Matrix Model

Not Applicable

Not Applicable

Not Applicable

Not Applicable

Not Applicable

Not Applicable

X

Not Applicable

12-Step Facilitation Therapy

X

Not Applicable

Not Applicable

Not Applicable

Not Applicable

Not Applicable

X

X

Source: Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition)

Leverage digital therapeutics where possible

Over the past several years, a variety of digital therapeutics have been developed that utilize phone app technology to deliver CM, CBT, texting, video conferencing, and other recovery-supportive resources. These apps require few additional clinic resources and can serve as staff-extenders. Some of the digital therapeutics are authorized by the U.S. Food and Drug Administration and can be prescribed by physicians. Apps to support CM are commercially available and streamline the process of random remote drug testing, tracking patient outcomes, and electronically depositing financial rewards on a debit card. Phone and computer-based mobile applications have the potential to enhance the ability of integrated primary care practices to implement CM in a manner compliant with the HHS Office of Inspector General (OIG) rules.

Examples of these apps include:

Reset-O

DynamiCare

WeConnect

Motiv8

CHESS

The topic of apps deserves more serious and detailed treatment, which we intend to provide on The Academy Portal at a later time. In the interim, we invite you to review other AHRQ work in this area.65, 66

Screen and Treat Co-Occurring Mental Health Problems

Co-occurring mental health problems are common in patients with substance use disorders and polysubstance use. In the National Comorbidity study from 1990,67 over half of adults with a substance use disorder were also affected by a mental disorder. There are several reasons for this overlap4 including the fact there is a common set of risk factors for the development of mental health and substance use problems, including genetics, epigenetics, brain region involvement, environmental influences, stress, trauma, and adverse childhood experiences. In addition, we see mental illness contributing to drug use, which some people may use as a form of self-medication. Conversely, we see substance use contributing to the development of mental illness.

Mental illness can negatively impact outcomes in the treatment of substance use disorders, including increasing the risk for relapse68 and dropping out of treatment.69 Thus, screening and treating co-occurring mental health disorders should be part of SUD treatment in order to increase the likelihood of SUD treatment success,70 although sometimes the effect is modest.71 Therefore it is recommended72 that both a person's mental and substance use disorders be treated at the same time, ideally by the same integrated multidisciplinary team. Treating one disorder before addressing the other disorder will likely undermine the patient's ability to improve from either type of problem.69, 73-77 By offering fully integrated services, coordination of care, and consistent treatment, goal messaging is achievable.

Screening and diagnosing mental health disorders in the context of polysubstance use

Screening and diagnosing mental health disorders within the context of SUD is challenging due to substance-induced psychiatric symptoms. Here are some key practice tips to sorting out a co-occurring disorder.

  • Use validated screeners,78 like the PHQ-9 for depression, the GAD-7 for anxiety, the PC-PTSD for PTSD, and the ASRS for ADHD are good places to start.
  • Screening should occur after a person is through their acute withdrawal and/or within 2-4 weeks after having been stabilized.
  • Ongoing substance use should not indefinitely delay screening and diagnosing a mental health disorder. In some cases, like ADHD and PTSD, treatment of the co-occurring mental health disorder can help patients stay in treatment longer70 and have fewer substance use and mental health symptoms.79
  • Psychiatric consultation should be available for diagnostic clarification.

Assess for suicidal ideations at the beginning of engagement and throughout treatment

Substance use places people at higher risk for suicide. In a 2020 study of a sample of the general U.S. population80 across 8 states and after taking into account age, gender, poverty level, education, and psychiatric diagnoses, people with an alcohol use disorder were at 6 times the risk of dying by suicide compared to the general population. People with a drug use disorder were at 5 times the risk of dying by suicide versus the general population. If people used both alcohol and drugs, the risk of dying by suicide was 11 times as high as in the general population. Developing a clinic-wide strategy for assessing suicide risk and then developing a safety plan is recommended. Below are some tips for such a program:

  • The Columbia-Suicide Severity Rating Scale (C-SSRS)81 is the recommended tool to assess suicide risk. This 6-question tool has been widely studied and validated in multiple countries and languages. It is available in over 140 country-specific languages. It is the only tool that assesses for intensity, frequency, and changes of suicidal ideation over time.
  • Relying on the 9th question of the PHQ-9 to screen for suicide risk is insufficient as it results in too many false positives and does not assess current suicidal plans or intent.82 If the PHQ-9 is to be relied on for preliminary assessment of suicide risk, a follow-up questionnaire, like the C-SSRS, should be used for a more complete assessment.
  • Further information on addressing suicidal thoughts and behaviors in substance use treatment can be found here: Substance Abuse and Mental Health Services Administration (SAMHSA) - Addressing Suicidal Thoughts and Behaviors in Substance Abuse Treatment – (858 KB) and The Colombia Lighthouse Project.

What is the best model of care for delivering integrated co-occurring treatment?

In general, a multidisciplinary care team is helpful to provide integrated treatment of co-occurring disorders in a primary care setting. This is due to the need to support both psychosocial interventions and deal with care management issues that will arise. Evidence also indicates that team-based care improves team morale and reduces staff burnout and compassion fatigue83 . Picking and choosing some of the interventions described above is a great place to start. Incorporating them into your existing integrated behavioral health care team is doable, but you'll need to take into account some of the considerations below. Current research is ongoing around ability and utility of treating co-occurring substance use and other mental health disorders within an integrated behavioral health setting.84

Does your integrated behavioral health team have the skill set and knowledge base to address both substance use and mental health problems?

  • Delivering fully integrated care will be dependent on the baseline knowledge and skillset of your behavioral health team. Knowledge around both therapeutic interventions and medications are needed.
  • Training to improve your team's knowledge base can be found across the internet at places like: Providers Clinical Support Center (PCSS), American Society of Addiction Medicine (ASAM), SAMSHA, Federally funded Mental Health Technology Transfer Centers (MHTTC), Addiction Technology Transfer Centers (ATTC),85-88 as well as state- and university-funded programs like Extension for Community Healthcare Outcomes (ECHO) programs.85-87
  • Oftentimes it is essential to bring in an expert consultant in addiction psychiatry or addiction medicine to help in expanding your team's scope of practice and to help with providing patient care.

What might be the impact of expanding the scope of my existing integrated care team to treat both substance use and other mental health disorders?

Treating patients with polysubstance use and co-occurring mental health disorders often requires more time and resources to track down patients from no-shows, attend to drop-in visits, and navigate some of the extra needs of this population, such as legal and housing needs. This can quickly overwhelm existing resources of the mental health team, who may be having a hard time keeping up with the typical referrals. Giving more time for care management and care coordination efforts is often needed.

Is it acceptable to network with specialty clinics and providers to support treating a person's co-occurring polysubstance use?

Yes. While fully integrated treatment for co-occurring disorders is the ideal, not all clinics will be able to provide this level of care. Thus, building out networks of community specialists to refer to and coordinate care with should be done. This will take time and effort to develop and maintain and support the necessary level of care coordination around treatment goals.

For further reading on developing your team to deliver integrated treatment for co-occurring disorders see the SAMSHA Integrated Treatment for Co-Occurring Disorders.

References

1. Substance Abuse and Mental Health Services Administration (SAMHSA). Treating Concurrent Substance Use Among Adults. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2021. Report No.: SAMHSA Publication No. EP21-06-02-002. https://store.samhsa.gov/sites/default/files/SAMHSA_Digital_Download/PEP21-06-02-002.pdf. Accessed May 16, 2022.

2. McCance-Katz EF. The National Survey on Drug Use and Health: 2019. Rockville, MD: Substance Abuse and Mental Health Services Administration, U.S. Department of Health and Human Services; 2020. https://www.samhsa.gov/data/sites/default/files/reports/rpt29392/Assistant-Secretary-nsduh2019_presentation/Assistant-Secretary-nsduh2019_presentation.pdf. Accessed May 16, 2022.

3. Lopez-Quintero C, Pérez de los Cobos J, Hasin DS, Okuda M, Wang S, Grant BF, et al. Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug and alcohol dependence. 2011;115(1-2):120-30. https://www.doi.org/10.1016/j.drugalcdep.2010.11.004. Accessed.

4. Common Comorbidities with Substance Use Disorders Research Report. Bethesda, MD: National Institutes on Drug Abuse (US); 2020. https://www.ncbi.nlm.nih.gov/books/NBK571451/pdf/Bookshelf_NBK571451.pdf. Accessed May 16, 2022.

5. Hassan AN, Le Foll B. Polydrug use disorders in individuals with opioid use disorder. Drug Alcohol Depend. 2019;198:28-33. https://www.doi.org/10.1016/j.drugalcdep.2019.01.031. Accessed May 16, 2022.

6. Bhalla IP, Stefanovics EA, Rosenheck RA. Clinical Epidemiology of Single Versus Multiple Substance Use Disorders: Polysubstance Use Disorder. Med Care. 2017;55 Suppl 9 Suppl 2:S24-s32. https://www.doi.org/10.1097/mlr.0000000000000731. Accessed May 16, 2022.

7. Crummy EA, O'Neal TJ, Baskin BM, Ferguson SM. One Is Not Enough: Understanding and Modeling Polysubstance Use. Front Neurosci. 2020;14:569. https://www.doi.org/10.3389/fnins.2020.00569. Accessed May 16, 2022.

8. Franklyn AM, Eibl JK, Gauthier GJ, Marsh DC. The impact of cannabis use on patients enrolled in opioid agonist therapy in Ontario, Canada. PLoS One. 2017;12(11):e0187633. https://www.doi.org/10.1371/journal.pone.0187633. Accessed.

9. Tsui JI, Mayfield J, Speaker EC, Yakup S, Ries R, Funai H, et al. Association between methamphetamine use and retention among patients with opioid use disorders treated with buprenorphine. J Subst Abuse Treat. 2020;109:80-5. https://www.doi.org/10.1016/j.jsat.2019.10.005. Accessed May 16, 2022.

10. Coffin PO, Galea S, Ahern J, Leon AC, Vlahov D, Tardiff K. Opiates, cocaine and alcohol combinations in accidental drug overdose deaths in New York City, 1990-98. Addiction. 2003;98(6):739-47. https://www.doi.org/10.1046/j.1360-0443.2003.00376.x. Accessed May 16, 2022.

11. Dillon P, Copeland J, Jansen K. Patterns of use and harms associated with non-medical ketamine use. Drug Alcohol Depend. 2003;69(1):23-8. https://www.doi.org/10.1016/s0376-8716(02)00243-0. Accessed.

12. O'Donnell J, Gladden RM, Mattson CL, Hunter CT, Davis NL. Vital Signs: Characteristics of Drug Overdose Deaths Involving Opioids and Stimulants - 24 States and the District of Columbia, January-June 2019. MMWR Morb Mortal Wkly Rep. 2020;69(35):1189-97. https://www.doi.org/10.15585/mmwr.mm6935a1. Accessed May 16, 2022.

13. Shiue KY, Austin AE, Proescholdbell S, Cox ME, Aurelius M, Naumann RB. Literal text analysis of poly-class and polydrug overdose deaths in North Carolina, 2015-2019. Drug Alcohol Depend. 2021;228:109048. https://www.doi.org/10.1016/j.drugalcdep.2021.109048. Accessed.

14. Abuse S, Mental Health Services Administration, General OotS. Reports of the Surgeon General. Facing Addiction in America: The Surgeon General's Report on Alcohol, Drugs, and Health. Washington, DC: US Department of Health and Human Services; 2016. https://www.ncbi.nlm.nih.gov/books/NBK424857. Accessed May 16, 2022.

15. Olfson M, Zhang V, Schoenbaum M, King M. Buprenorphine Treatment By Primary Care Providers, Psychiatrists, Addiction Specialists, And Others. Health Aff (Millwood). 2020;39(6):984-92. https://www.doi.org/10.1377/hlthaff.2019.01622. Accessed May 16, 2022.

16. Krist AH, Davidson KW, Mangione CM, Barry MJ, Cabana M, Caughey AB, et al. Screening for Unhealthy Drug Use: US Preventive Services Task Force Recommendation Statement. JAMA. 2020;323(22):2301-9. https://www.doi.org/10.1001/jama.2020.8020. Accessed May 16, 2022.

17. Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, et al. Screening and Behavioral Counseling Interventions to Reduce Unhealthy Alcohol Use in Adolescents and Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(18):1899-909. https://www.doi.org/10.1001/jama.2018.16789. Accessed May 16, 2022.

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