Medically Reviewed

Mixing Prescription Opioids with Other Substances: Other Opioids, Marijuana, Benzodiazepines, and Stimulants

5 min read · 7 sections
Polysubstance use involves the use of two or more substances at the same time or within a short time of each other.1 Research suggests that concurrent use of other substances among people who use opioids is relatively common. For example, in one study that examined polysubstance use in individuals who used heroin and misused prescription opioids, researchers found higher rates of opioid use in people who also used cocaine or methamphetamine.1 Additionally, studies conducted over a 15-year period from 2001-2016 indicate that nearly 80% of fatal opioid overdoses involved another substance. In fact, 78% involved another opioid, 21.6% involved cocaine, 11.1% involved alcohol, and 5.4% involved a psychostimulant other than cocaine.1
What you will learn:
What opioids are
The dangers of mixing opioids with other substances
The potential consequences and dangers of polysubstance use involving opioids
How to find treatment for polysubstance addiction

What are Opioids?

Opioids are a class of drugs that include both illicit substances like heroin as well as prescription painkillers and analgesics, such as fentanyl, oxycodone, hydrocodone, and morphine.2 

All opioids produce their effects and diminish the body’s perception of pain by binding to specific opioid receptors located in the brain, spinal cord, and gastrointestinal tract. This opioid receptor activation is associated with a range of effects, including heightened dopamine activity in the brain’s reward centers, which can make some individuals want to continue opioid use.3

Prescription opioids are most often prescribed to treat severe and/or chronic pain but may have some additional therapeutic uses, such as treating a cough or diarrhea.3 Commonly prescribed opioids include:3 

When taken as prescribed under a doctor’s supervision–and for a short period of time–prescription opioids are generally safe. However, like other prescribed medications, there is the potential for misuse if used in ways other than prescribed–such as taking more than was prescribed, taking someone else’s medication, or using the drug to get high.3 Additionally, individuals may misuse opioids in combination with other substances.1,3

Mixing prescription opioids and other substances, including alcohol, illicit opioids, benzodiazepines (e.g., Xanax), stimulants, and a wide array of other substances can increase the risk of adverse effects, relapse after treatment, and overdose.4

Adverse Effects of Opioids 

Besides the pain-relieving properties, opioids can also cause a range of unpleasant and potentially dangerous effects, including:3,5

  • Drowsiness.
  • Confusion.
  • Nausea.
  • Constipation.
  • Slowed breathing.
  • Dizziness.
  • Increased sensitivity to pain.
  • Depression.
  • Itching and sweating.
  • Euphoria.
  • Tolerance, meaning you need to take more of the drug to experience the same pain relief.
  • Physical dependence, meaning your body adapts to the presence of the drug and you experience withdrawal symptoms when you stop using it.
  • Addiction, or opioid use disorder.

Dangers of Mixing Prescription Opioids with Other Opioids

Combining prescription opioids, such as hydrocodone or oxycodone, with other prescription opioids or illicit opioids like heroin or illicitly-manufactured fentanyl is a dangerous practice that can increase the risk of adverse effects and lead to potentially fatal consequences.1 

Combining opioids can potentiate the adverse effects of opioids, such as dangerously slowed or stopped breathing and unconsciousness as well as an increased risk of fatal overdose.1,6

It’s important to know that illicitly-manufactured fentanyl is dangerous due to its potency–it is 50-100 times more potent than morphine or heroin and is a major contributor to the overdose epidemic in the United States. Fentanyl is especially dangerous if it’s combined with prescription opioids or street drugs like heroin, and it is sometimes added to counterfeit pills and other street drugs without the purchaser’s knowledge.6

Dangers of Mixing Prescription Opioids with Weed  

People may use marijuana for different reasons, including pain management, but it can also produce a variety of undesirable effects, such as drowsiness, slowed reaction time, balance and coordination problems, increased heart rate, anxiety, and problems with learning.7 Research suggests that using opioids like hydrocodone or oxycodone with weed may increase the risk of opioid misuse.8 

In fact, studies indicate that about 25% of opioid-related emergency department visits also involved marijuana.1 And another one found that individuals who use marijuana were far more likely to also use opioids for non-medical purposes than individuals who did not use marijuana.9

Additionally, some research suggests that combining prescription opioids, such as Vicodin (which has been discontinued, but there are generic equivalents) or Percocet with marijuana, may be associated with mental health problems, such as anxiety or depression; opioid dependence; and the development of opioid use disorder (OUD).10,11

Dangers of Mixing Prescription Opioids with Benzodiazepines 

Benzodiazepines, also known as benzos, include drugs like alprazolam (Xanax), diazepam (Valium, which has been discontinued), and lorazepam (Ativan).7 Often prescribed to treat anxiety or sleep disorders, these drugs are central nervous system (CNS) depressants, which means that they slow down brain activity and produce a calming effect.7,12

In 2016, the U.S. Food and Drug Administration (FDA) issued a boxed warning, their strongest warning, to the labels of prescription opioids, benzodiazepines, and other CNS depressants, highlighting the potential serious side effects–including slowed breathing and death–associated with the concomitant use of opioids and benzodiazepines.13

The combination of benzos, such as Xanax, and any opioids can lead to dangerous over-sedation, profound respiratory depression, and deadly overdose.112 In 2021, nearly 75% of the 12,500 overdose deaths involving benzodiazepines also involved opioids.14

Consequences Associated with Mixing Prescription Opioids and Stimulants

Stimulants, which include prescription medications such as dextroamphetamine, methylphenidate (Concerta, Ritalin), amphetamine (Adderall), dextroamphetamine (Dexedrine) and methamphetamine (Desoxyn), as well as illegal drugs like crystal meth and cocaine, are central nervous system activating drugs that can increase alertness, motivation, attention, and energy, and also raise blood pressure, breathing rate, and heart rate.7,15

Studies indicate that intentional concomitant use of the two substances may be attributed to attempting to balance the effects of each drug and to manage the symptoms of opioid withdrawal.1

Unfortunately, the co-use of stimulants and opioids, a practice that can increase the risk of medical complications and overdose, seems to be trending upwards in the United States.16 In fact, one study found that individuals who used opioids and stimulants together were twice as likely to experience a fatal overdose compared to people who used opioids alone.17 And for more than 2 decades, the number of overdose deaths involving stimulants and opioids has increased significantly.14 One study involving 24 states and the District of Columbia found that nearly one-third of overdose deaths involved opioids and stimulants.18 

Additionally, in 2018, 74.2% of cocaine-related overdose deaths and 50.5% of psychostimulant-related overdose deaths involved opioids.16

Furthermore, both stimulants and opioids carry a risk of physiological dependence and addiction on their own. Co-use of these substances may alter the brain and behavior differently than compared to the use of either drug alone. In fact, studies indicate that the polysubstance use of morphine and methamphetamine can result in greater rewarding effects and higher reinforcing effects than either drug produces on its own, which can make stopping substance use more difficult.19

Treatment for Polysubstance Addiction

If you or a loved one struggle with controlling drug use or controlling polysubstance use, treatment can help. Effective, evidence-based care for addiction may involve multiple components, such as withdrawal management, psychological and FDA-approved pharmacological treatment, monitoring, and support–all as part of a comprehensive, individualized treatment plan.20

While there are no medications to treat some substance use disorders like stimulant use disorder or marijuana use disorder, medications such as buprenorphine or methadone may be given to individuals with OUD during detox to ease withdrawal symptoms and cravings and to help them stay on track with their recovery.21-23

In addition to medication, behavioral therapies can help people with substance use disorders make healthy life changes and develop the skills necessary to maintain a substance-free lifestyle.20 Therapies used in the treatment for OUD and other substance use disorders may include:20

  • Cognitive-behavioral therapy (CBT). CBT helps individuals identify and change unhelpful thoughts and behaviors that contribute to substance use and build coping skills to prevent relapse.
  • Motivational interviewing (MI). Designed to help individuals explore and resolve their ambivalence about changing their substance use and related behaviors, MI also helps them increase their motivation to work on making positive changes.
  • Contingency management. Based on principles of positive reinforcement, contingency management provides rewards when individuals achieve target goals, such as negative drug tests.

Medical detox, which helps people safely and comfortably undergo medically supervised withdrawal, is often the first step. It typically involves medication, support, and monitoring to ensure a person’s safety as they return to a medically stable state.24

Detox is generally one part of a more comprehensive treatment plan, which may involve inpatient or outpatient rehab.24 A thorough assessment–performed by a primary care physician, mental healthcare provider, or team of addiction treatment professionals–determines the level of care that’s right for an individual’s needs.25

Inpatient rehab involves living onsite for the duration of treatment, where the individual receives 24/7 support and care and can fully focus on their recovery without the distractions of daily life.25 

Outpatient treatment, on the other hand, allows individuals to live at home and travel to rehab on a regular schedule to participate in treatment. Individuals can maintain their responsibilities at home, work, or school in outpatient programs–many of which offer flexible schedules, such as evening or weekend programs.25 

Regardless of the setting, treatment for OUD and polysubstance addiction provides individuals with medication for opioid use disorder, behavioral therapies–such as those mentioned above–in both group and individual settings, and mutual-help groups like Narcotics Anonymous (NA), where they can benefit from the support and camaraderie of others who are also in recovery.20

If you or a loved one are ready to break the cycle of addiction and stop substance use, reach out to American Addiction Centers (AAC) at . Let one of our compassionate and knowledgeable admissions navigators–many of whom are in recovery–listen to your story, answer your questions, explain your options, and help you get started on your recovery journey.

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