Polysubstance use

Understanding polysubstance abuse

Polysubstance abuse is the use of two or more drugs (or alcohol) together or in a short period of time. Essentially, a user will combine substances to enhance or change a drug’s effects. This can mean using two or more substances at the same time or using additional substances before the effects of a previously used substance wears off. Polysubstance abuse can occur with both legal and illegal substances, including alcohol and prescription drugs. Combining substances can create interactions, leading to unexpected and dangerous results.

Is polysubstance abuse safe?

While using one drug can be dangerous and result in overdose, combining drugs also is extremely unsafe. Whether intentional or accidental, the practice should be avoided. According to the Centers for Disease Control (CDC), combining drugs can make the effects of a substance stronger, more unpredictable and deadlier than when used alone. 


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Polysubstance use can be accidental or intentional. Though it can be dangerous and even toxic, sometimes substance users will mix drugs to alter or increase the effects of a substance. In other instances, substance users may be unaware that the drug they are using was cut with a second drug. For example, fentanyl is increasingly being used as a cutting agent for drugs like cocaine to make it appear more powerful. Unfortunately, even a miniscule amount of the potent opioid can lead to overdose and death in unsuspecting users. As a result, many unintentional polysubstance users unknowingly ingest fentanyl. Other accidental polysubstance use occurs when a person takes a prescription medication and mixes it with another medication or substance like alcohol without knowing the potential for harmful interactions.


Risks of polysubstance abuse

Effects of polysubstance abuse

Polysubstance abuse can result in a number of negative consequences. More than half of patients hospitalized for drug use consume two or more substances, according to one study. Patterns of use may vary depending on the individual. For instance, some primarily consume alcohol but may also use other drugs, while another individual may be dependent on opioids and occasionally combine them with other substances. Still, combining drugs, or drugs and alcohol presents important health risks. Drug overdose accounts for approximately 38% of accidental deaths caused by unintentional and preventable injuries in the U.S each year., a majority of which involve more than one substance. Although the opioid epidemic has been a huge driver of overdose deaths in recent years, polysubstance abuse is nothing new. For example, evidence of speedball use dates back to the 1950s. Many heroin overdose deaths in San Francisco in the 1970s also involved alcohol. More recently, a 2017 study found that the average number of drugs found in toxicology reports for opioid overdoses was 6. Most commonly, this meant alcohol, amphetamines or multiple opioids. While the issue of polysubstance use is not novel, it puts users at risk for addiction, overdose and death.

Prescription drugs and polysubstance abuse

Prescription drug opioids

Many wonder if it is safe to mix prescription drugs. When combined, prescription drugs, and even some over-the-counter medications, can interact causing adverse reactions including overdose. For this reason, a doctor should always be consulted to ensure that medications can be used together safely. Do not assume that your doctor is aware of all medications you are taking. Before using a new medication, it is important to check with your medical provider to ensure there are no dangerous interactions between substances. Similarly, combining medications with alcohol or other illegal drugs can also create adverse effects, even causing overdose in some instances. It is important to let your doctor know about all substances that you are using to avoid unanticipated and dangerous interactions.

The effects of mixing drugs

As mentioned, mixing substances can be extremely dangerous, leading to unintended results, including overdose. Often, combining drugs together can be unpredictable. While the specific effects of polysubstance use can depend on the individual, their health, the substances and dosage taken, in addition to many other factors, there are some general concepts that can help you understand polysubstance abuse. 

Different types of drugs have distinct effects on the body and brain. Drugs are often classified by their effect on the Central Nervous System (CNS). For example, stimulants speed up the functioning of the CNS, while depressants slow it down. But what happens when you mix different drugs or different types of drugs together?

Stimulant polysubstance abuse

Examples: Cocaine, MDMA (ecstasy), Amphetamines, Methamphetamine, Speed, Ice

Stimulants may be used legally and illegally, depending on the substance and whether or not the user has a valid prescription. As mentioned, stimulants, also known as uppers, speed up the CNS. Stimulants can increase a person’s heart rate and blood pressure causing several dangerous side effects.

Though taking one stimulant can certainly cause overdose, combining stimulants can further increase this risk. Stimulant polysubstance abuse may result in the heart attack, brain injury, stroke, liver damage, overdose and even death. While there are other indications to look for, a few common signs of stimulant overdose include: 

  • Rapid or shallow breathing
  • Increased body temperature
  • Increased heart rate
  • Dizziness
  • Nausea
  • Seizure
  • Tremors

Depressant polysubstance abuse

Examples: Alcohol (Ethanol), Benzodiazepine,  Sedative Hypnotics, Barbiturates, GHB, Rohypnol

Like stimulants, depressants work by affecting the CNS. Instead of speeding things up, they slow down the messaging between the brain and the body. This can lead to feelings of relaxation and lowered inhibition, limiting a person’s ability to respond to unexpected situations. Depressants should only be taken with a valid prescription. Some depressants are prescribed and used legally, while others are taken off prescription or produced, sold or used illegally. Mixing depressants can increase the risk of overdose and death, as can taking too large of a dose. Breathing may slow or stop, preventing oxygen from getting to the brain. Depressant polysubstance abuse can result in organ damage, brain damage, overdose and death. A few common signs of depressant overdose include:

  • Slowed or stopped breathing and/or heart rate
  • Confusion, dizziness,  passing out
  • Loss of motor coordination
  • Slurred speech, weakness, headache, lightheadedness
  • Nausea, vomiting

Opioid polysubstance abuse

Examples: Oxycodone, Hydrocodone, Morphine, Fentanyl, Tramadol and Heroin  

Opioids are drugs that are generally prescribed for pain management, but are also often diverted, counterfeit and abused. Heroin is an opioid made from the poppy plant that is produced, sold and abused illegally. Even when prescribed and used legally, opioids can be quite addictive, causing users to quickly build a tolerance and develop cravings. Opioid medications affect the opioid receptors in the brain and can cause feelings of relaxation and sleepiness. When two or more opioids are combined or too high a dosage is ingested, these effects can be heightened, leading to slowed breathing, decreased heart rate and a risk of death. Combining opioids certainly increases this possibility. Over the past two decades, opioids have been linked to over 840,000 overdose deaths in the United States alone. Fentynal, which is 50 to 100 times more potent than morphine, is especially dangerous in this respect. Increasingly, illegally sold opioids are being mixed with fentanyl, causing users to overdose without even being aware they have ingested the powerful substance.  Polysubstance opioid abuse can result in loss of brain function and brain injury, respiratory, gastrointestinal, musculoskeletal, cardiovascular, immune, endocrine, and central nervous system damage, overdose and deathNaloxone is a drug that can be used to reverse an opioid overdose if applied quickly and correctly. Keep naloxone on hand, and know how to use it in case of an opioid overdose. A few common signs of opioid overdose include: 

  • Pale fingers
  • Pallid skin
  • Blue or purplish lips
  • Slowed or stopped breathing
  • Slowed or stopped heartbeat
  • Vomiting or gurgling sounds
  • Inability to speak or be awakened

Mixing stimulants and depressants

Combining stimulants and depressants can be extremely unsafe. While some might believe depressants and stimulants balance each others’ effects out, this is false. Using a stimulant and a depressant together can cause unpredictable results and increase the odds of overdose. One substance might be masking the true effects of the other on the CNS. This can cause users to be unaware of what is truly happening in their body or to increase their dosage, leading to overdose and even death. If you have been prescribed stimulants and depressants by a doctor, check with your medical provider before combining them or using them with alcohol, medications or other drugs. Make sure that there are no dangerous interactions and be aware of all risks.

Mixing opioids and other drugs

Using opioids with other substances can be extremely hazardous. The already dangerous and addictive opioid becomes even more risky when combined with other drugs. Some users will intentionally mix opioids with other substances. For instance, speed-balling, or taking opioids and stimulants together, is a practice among some heavy drug users.  However, some drug users may be unaware that the substance they are ingesting is mixed with an opioid like fentanyl, putting them at extreme risk for overdose. 2 out of 3 opioid overdose deaths in 2018 involved a synthetic opioid such as fentanyl, which is frequently used to cut other drugs. Mixing prescription drugs and opioids, with or without a prescription can also be dangerous. One example of an unsafe combination is benzodiazepines and opioids. Both depress CNS functioning and when used together, sedation and depressed breathing can lead to overdose. One study found overdose death rates to be 10 times higher in patients receiving both medications compared to those who only received opioids. All in all, opioids can be extremely risky on their own, and combining them with other substances may only increase the odds of overdose and death.

Signs of polysubstance abuse & addiction

It is important to be able to recognize the signs of addiction. Whether a person is using one or multiple substances, substance abuse can be extremely dangerous and lead to overdose. Here are a few common signs that could indicate that your loved one may be struggling with an SUD:

  • Changes to their appearance: Significant changes in weight, an unkempt appearance, strange smells, tremors, slurred speech, red eyes and dilated pupils are all common symptoms of addiction.
  • Problems at work: Missing work, showing less interest in job/school performance or hobbies, and trouble maintaining a steady job can be indications of a substance abuse issue.
  • Trouble with money: Maintaining a drug or alcohol habit can be quite costly. Constantly needing money, a sudden inability to pay bills, and missing cash or valuables could be evidence of an SUD. 
  • Behavior changes: Changes in personality, unexpected mood swings, bouts of extreme lethargy or energy, irritability, disappearing for periods of time and secretiveness can all be indicators of addiction.

Remember, the specific symptoms of a substance use disorder can vary from person to person and may depend on the type(s) of drug that they are abusing. If you are concerned about yourself or a loved one’s use of substances, whether they are abusing one substance or multiple, it may be time to seek help.

Comprehensive treatment for polysubstance abuse

If you or a loved one is struggling with polysubstance abuse, or substance abuse in general, treatment may be the right option. Many try to stop using drugs and alcohol on their own. While they may be successful for a short period of time, research shows longer stays in  treatment programs increase the odds of maintaining long-term sobriety. This is because those who struggle with addiction often have underlying issues and traumas that need to be addressed. Moreover, participants in treatment programs are able to acquire the life skills necessary to support a healthy, substance-free lifestyle.

What to look for in a polysubstance dependence treatment program 

Liberty Ranch Addiction Treatment

A certified, evidence-based addiction treatment program can be critical for those struggling with substance use disorders. Strong programs should offer a variety of research-backed interventions including individual and group counseling, behavioral therapies, family/couples therapy, and life skills training. A good program will work with a qualified, multidisciplinary team to treat clients’ underlying issues, including comorbid conditions. 

Liberty Ranch Rehabilitation Center offers clients a comprehensive Intensive Outpatient Program (IOP) based around addiction sciences and 12-step principles. We recognize that getting sober is just the first step in the recovery process. With 25 years of experience in addiction recovery, Liberty Ranch helps clients build the behavioral and emotional tools needed to sustain long-term sobriety. To truly heal and build a sober lifestyle, it is equally important for those with addictions to address the underlying issues that caused the disorder to develop in the first place. Liberty Ranch’s trained addiction specialists help participants build life skills, work through issues and develop functional ways of reacting and behaving that promote long-term sobriety from substances. 


Learn more about treatment options

If you are considering  addiction treatment for yourself or someone in your life, now is the time to take action. Addiction is a deadly disease that has taken too many lives, broken up families and destroyed futures. Liberty Ranch offers free consultations. Call 888-387-1531 to talk to a specialist that can let you know about the treatment options available and help you select the right program.


 In light of the many complex issues those with SUDs face, Liberty Ranch takes a holistic approach to treating addiction, helping clients build a healthy, sustainable, substance-free lifestyle. Graduates gain the tools to cope with negative emotions and triggers, allowing them to build more successful and productive lives rooted in recovery.

  •  The IOP program provides and/or works with partners to offer partial hospitalization, outpatient care, psychiatric evaluation services, and family counseling services.
  • Addressing comorbid conditions like depression, anxiety, anorexia and other disorders can be a critical element of treatment. The integrative IOP program serves clients struggling with comorbid conditions, as substance use disorders often occur in conjunction with other mental health issues that influence a person’s recovery. 
  • Liberty Ranch also offers a specialized program for women, who often face several additional challenges when navigating recovery. The Liberty Ranch Women’s Program addresses the traditional scope of treatment, while considering the specific challenges unique to women with addictions.