Effects of Mixing Many Painkillers

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  1. Effects of Combining Opiate Medications
  2. Why Do Some Users Combine Opiate Medications?
  3. What Does the Research Say?

What Happens When You Mix Many Painkillers?

Painkillers – or opioid analgesics – are some of the most commonly abused prescription medications. They bind to opioid receptors in the brain to suppress or alter the perception of pain (analgesia), but the usefulness of their analgesic effects can be overwhelmed by other side effects and complications that may develop due to chronic use and/or abuse.
What Happens When You Mix Many Painkillers?

Common side effects of opioid administration include:

  • Sedation.
  • Dizziness.
  • Nausea.
  • Vomiting.
  • Constipation.
  • Physical dependence.
  • Tolerance.
  • Respiratory depression.

As opioid use rises, it becomes increasingly important that we better understand the neurological and behavioral effects of combining these drugs – especially given the known risks of opioid dependence, addiction, cognitive impairment, and hyperalgesia (increased sensitivity to pain).


Opioid analgesics are some of the most potent and widely used painkillers. Use of such painkillers, including mixed use involving more than one of these, is not uncommon.

Statistics and Prevalence

  • Painkillers are the second most commonly abused illicit substances in USA.
  • The results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) suggest that young adults in the age range of 18-29 years had the highest rates of non-medical use of prescription opioids with 7.4% reporting such use.
  • Monitoring the Future Survey in USA revealed that the non medical use of prescription opioids had doubled among high school seniors between the years 1991 to 2007. 
  • The Prescription Drug Overdose Data from Centers for Disease Control and Prevention reports that 71.3% of the prescription drug overdose related deaths involved opioid painkillers.
  • Additionally, opioid painkillers were involved in 420,400 Emergency Department visits in the year 2013.

Effects of Combining Opiate Medications

man looking drowsy

Some of the opiate analgesics are distinct from from each other with regards to their pharmacokinetic (how the body handles these painkillers) and pharmacodynamic (what the painkillers do to the body) profile.

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When used in combination, the effects experienced by the user shall depend on the properties of the individual opiate and the possible interaction between various opiates.

Some of the adverse effects that can be exacerbated by combined use include:

  • Hyperalgesia (also referred to as hyperalgia) is an increased sensitivity to pain. This usually happens at some point after the initially-prescribed doses of the opioid have been escalated. The exact underlying mechanism of this sensitization is still a topic of research. The phenomenon can be quite a troublesome development as it may potentiate a compulsive cycle of drug taking.
  • Sedation or respiratory suppression: Some of the sedation and drowsiness associated with opioid use is thought to be imparted by their anticholinergic properties. Although tolerance to these side effects often develops, combining two or more opioids can lead to dangerous dose escalation and suppress respiration to the point of coma or even death.
  • Substance use and psychiatric comorbidity: Increased rates of psychiatric comorbidities, like depression and anxiety, have been well documented in long-term prescription opioid users relative to individuals who do not use opioids. The risk is exacerbated in the case of multiple opioid abuse. The following assertions can be made about taking multiple opioid painkillers and psychiatric problems:
    • Unrecognized psychological problems can increase the intensity and experience of chronic pain, therefore leading a person to abuse their prescription or combine multiple medications.
    • Chronic pain can disrupt a person’s quality of life, leading to psychological conditions that enhance the likelihood of negative substance using tendencies.

Other potential adverse effects associated with opioid medication use include:

  • Overdose.
  • Fatal medication interactions.
  • Increased likelihood of contracting infectious diseases (should users begin to administer the drugs via injectable routes).
  • Engagement in other risky behaviors, including alcohol and other drug abuse.

Why Do Some Users Combine Opiate Medications?

As mentioned earlier, in spite of being grouped together as opioid analgesics some opioids differ from each other with respect to their metabolism in the body as well as the nature of the effects produced.

Due to distinct affinities for various opioid receptors, these specific opioid painkillers differ from each other in terms of latency of onset of action, peak analgesia, duration of action, and side effects.

Hence, besides the expectation of adding on to the analgesic and other desirable effects, one can mix opioid painkillers with an aim to:

  • Prolong duration of use.
  • Take care of breakthrough pain or discomfort.
  • Experience additional effects specific to different opioid painkillers.

Moreover, at times logistic factors such as availability and ease of access also shape the pattern of use of opioid painkillers in combination.

woman sitting on floor holding pillbox looking upset

What Does the Research Say?

Opioids exert their effects by acting on the mu, delta, or kappa receptors in the brain. The effects of each opioid differ based on their relative affinities for each receptor. Due to these differences, the individual clinical situations are often complicated and difficult to predict as effects are a result of various adaptations at the cellular and molecular level.

Medical Treatment

Medications to manage opioid addiction include:

  • Opioid agonists (e.g., methadone, buprenorphine).
  • Opioid antagonists (e.g., naloxone, naltrexone).
  • Medications for managing withdrawal symptoms (clonidine and anti-emetics).

Use of opioid maintenance therapy has been found to be effective for improved treatment retention and drug use reduction. Use of these medications has been found to be effective in improving treatment outcome among prescription opioid abusers as well. Similarly, it has been reported that naltrexone maintenance therapy, when combined with psychosocial therapy, is effective in discouraging drug abuse during treatment.

Psychological Treatment

It has been shown that certain psychosocial therapies and counseling strategies are also effective for management of addiction to prescription opioids. These include:

Psychological intervention in form of CBT, when offered as an adjunct to long term substitution therapy in the form of methadone and buprenorphine-naloxone, has been reported to be efficacious in improving retention in treatment among individuals with opioid addiction, in addition to improvements in clinical and social outcomes.

Use of contingency management as an adjunct has been found to be effective in improving retention rates on substitution therapy as well as naltrexone maintenance treatment for opioid addiction.

Inpatient Treatment

Both inpatient as well as outpatient treatment is available and has been found to be effective in management of opioid addiction.

Inpatient treatment is offered through a host of different domains. These include:

  • Publicly funded addiction treatment centers.
  • Private and luxury addiction treatment centers.
  • Executive addiction treatment centers.

Individuals with severe addiction, comorbid physical and mental disorders, poor social support, and past failed attempts at quitting from outpatient are best suited for residential inpatient treatment. Inpatient treatment also offers longer periods of direct contact with a treatment team and makes it relatively easy to stay away from the drugs due to their isolating nature. 

Residential inpatient treatment for addiction is offered through round the clock stay facilities. One remains at the treatment facility for the entire duration of the program.

Outpatient Treatment

Outpatient treatment is less intense than inpatient treatment; it may be beneficial if the severity of addiction is low and there are no debilitating physical or psychological problems.

The patient has to follow a regimen of psychological therapy and regularly scheduled visits with a medical practitioner, but the flexibility allows them to fulfill their obligations, like school or work.

Associated Social and Mental Health Problems

Abuse of prescription opioids is associated with significant costs to the society. Of the $8.6 billion lost due to prescription opioid abuse in USA, $4.6 billion were workplace costs and another $1.4 billion were criminal justice costs in the year 2001. 


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