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Understanding the Paradoxical Effect

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Medically Reviewed By: Diana Vo, LMFT

January 31, 2024

Table of Contents

The paradoxical effect occurs when a medication causes side effects in direct opposition to its intended outcome – an anti-nausea medication triggering sickness, for instance.

Paradoxical drug reactions are commonplace among people with mental health disorders, specifically attention-deficit hyperactivity disorder (ADHD).  The paradoxical effect of certain medications can also induce or aggravate a range of other conditions by delivering opposite outcomes to the desired outcomes.

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What is a Paradoxical Reaction?

What is the paradoxical reaction definition?

Firstly, this type of drug reaction delivers an outcome opposite to the expected outcome. 

More broadly, research indicates three distinct types of paradoxical drug reactions: 

  1. A paradoxical response when the drug is prescribed for an explicit purpose.
  2. A paradoxical response to the condition for which the medication is indicated when the medication is being used off-label (used for an alternative indication).
  3. A paradoxical response unrelated to the usual indication of the drug.

Paradoxical drug effects can be beneficial or adverse, depending on the circumstances. 

What causes paradoxical reactions, then? 

What Causes a Paradoxical Effect?

The mechanism of paradoxical drug reactions is not yet fully understood. One significant reason complicating this understanding is the fact that monitoring the transfer of single neurons in this area of the brain – the subcortical structure – is usually not possible. 

The paradoxical effect can occur in a wide range of drug classes, including:

  • Benzodiazepines
  • Stimulants
  • Barbiturates
  • Neurosteroids
  • Alcohol
  • inhalational anesthetics
  • Propofol

An evidence base shows that some paradoxical drug reactions are common, while others appear in single case reports.

In the above cases, paradoxical effects are associated with changes to the structure of GABA receptors. The subunits of these GABA receptors can remain unaltered, but the response to certain substances differs radically from the norm. 

One possible explanation for paradoxical drug reactions involves the concept of hormesis. Hormesis is a term toxicologists use to express biphasic dose-response. This response involves a low dose delivering beneficial effects, but a higher dose delivering adverse effects. 

Ionizing radiation is a practical example of hormesis in action. While deadly in high amounts due to the way it damages DNA and triggers mutations, lower doses of ionizing radiation can be used as an effective treatment for cancer. 

Some researchers, then, suggest that paradoxical drug reactions occur when the typical dosage for a medication lies beyond someone’s personal threshold for a beneficial response. While this theory can explain some types of paradoxical effects, there is insufficient evidence-based on human clinical trials, so this remains an unsubstantiated theory at present.

There are many additional factors that impact the way in which your body processes drugs. These include:

  • Drug tolerance
  • Genetics
  • State of body before taking drugs
  • Underlying infections or medical conditions

Most researchers hypothesize that no single mechanism applies to all paradoxical responses. This is largely due to the vast array of interactions that can trigger the paradoxical effect. While these events are still not fully understood, it is believed that paradoxical reactions do not present a significant risk to most people. Research in this area is vigorous and ongoing. 

Paradoxical Reaction Examples

Two of the most commonly reported examples of paradoxical drug reactions involve the following drugs:

  • Benzodiazepines
  • Stimulants


Benzodiazepines are often administered to induce sedation in patients. 

In the event of a paradoxical reaction benzodiazepine, symptoms include:

  • Excitement
  • Emotional release
  • Excessive movement
  • Increased talkativeness

This type of reaction is relatively rare, occurring in less than one in a hundred patients. 

As with other paradoxical events, the precise mechanism of paradoxical benzo reactions is unclear. 

The typical effects induced by benzos are as follows:

  • Sedative
  • Hypnotic
  • Muscle-relaxing
  • Anti-convulsant
  • Anxiolytic (anti-anxiety)

In some cases, though, these minor tranquilizers can cause the exact opposite of these effects in a classic paradoxical event.

Those susceptible to the paradoxical effect of benzo reactions often experience an increase in these areas:

  • Impulse control
  • Anxiety
  • Aggression
  • Disinhibition
  • Confusion
  • Agitation
  • Talkativeness
  • Violence

When paradoxical rage reactions are triggered by benzodiazepines, this occurs due to altered consciousness generating automatic behaviors like raw, uninhibited aggression. These paradoxical aggressive actions are possibly caused by a disinhibiting serotonergic mechanism.

While the mechanism underpinning paradoxical benzo effects remains unclear, these events appear linked to dosage, with higher doses increasing the likelihood of adverse and paradoxical reactions from benzos, according to this review of studies. 

Additionally, benzos can sometimes trigger paradoxical impairment of EEG readings in those with seizure disorders, per this study


Amphetamines belong to a class of psychoactive drugs classified as stimulants.

Paradoxical reactions infrequently occur in adults using stimulants in the form of paradoxical drowsiness

Stimulant medications like Ritalin and Adderall have a paradoxical effect on both children and adults with ADHD. For most people, taking stimulants induces hyperactivity. For those with ADHD, though, the opposite effects are triggered. Some children prescribed stimulant medications for attention-deficit hyperactivity disorder find problems with sleeping manifest, although hyperactivity is decreased, and the ability to focus is improved.

While researchers once assumed that stimulants only induced paradoxical calming effects in patients with ADHD, the consensus has now shifted. Recent studies show that low doses of stimulants help improve executive function and focus attention, in those both with and without ADHD. Paradoxical stimulant reactions, then, are dose-related.

Getting Help for Drug Addiction at Renaissance Recovery

Here at Renaissance Recovery, we specialize in the outpatient rehab for addiction for substance use disorder (the formal descriptor for drug addiction). 

If a standard outpatient program doesn’t offer you enough support or structure for your recovery, we also deliver IOPs (intensive outpatient programs) and PHPs (partial hospitalization programs) to give you the benefits of residential rehab with the restrictions or the cost. 

Our rehabs in Florida and California offer clients world-class addiction treatment care and we can provide guidance every step of the way.

Whichever program makes the right fit – we also offer dual diagnosis treatment for co-occurring disorders – you’ll have access to the following therapies:

  • Medication assisted treatment
  • Talk therapies like CBT or DBT
  • Group counseling
  • Individual counseling
  • Holistic therapies
  • Family therapy

Through this combination of research-based therapies, your treatment team will help you build a solid foundation for sober living. 

To start unchaining yourself from addiction, take the first vital step by reaching out to Renaissance Recovery at 866.330.9449.



At Renaissance Recovery our goal is to provide evidence-based treatment to as many individuals as possible. Give us a call today to verify your insurance coverage or to learn more about paying for addiction treatment.

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Joseph Gilmore has been in the addiction industry for three years with experience working for facilities all across the country. Connect with Joe on LinkedIn.

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