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Drug Tolerance Definition

/  Last Updated: 
August 17, 2023
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Drug tolerance definition is sometimes misunderstood, as the nature and development of the phenomena are quite complicated. Drug tolerance occurs due to prolonged consumption of medication: sedatives, stimulants, or painkillers.

After continuous intake of a prescription or recreational drug at a certain dose, a person's reaction to it dulls.

People who experience drug tolerance tend to misuse it and develop dependence which is followed by drug addiction.

Developing drug tolerance takes you a step closer to addiction and needing a drug use rebab program such the one we provide here in Thailand - regardless if the drug in question is a prescribed medication, or one bought on the streets.

Understanding the physical and psychological reaction to a particular drug will keep you on the safe side.

This article discusses:

  • Drug tolerance definition
  • Difference between tolerance and dependence
  • Types of tolerance
  • Drug tolerance risks
  • How to prevent drug tolerance

tolerance drug definition

What Is Tolerance to a Drug?

Before we state a definition of drug tolerance, it is necessary to point out that developing drug tolerance is not the same as developing a drug addiction.

Drug tolerance (medical definition) occurs when a person's body acclimates to a drug or alcohol - as a result, their tolerance decreases, and higher doses are required to attain the desired effect.

In simple terms, drug tolerance is when a person's body gets used to a regular intake of a prescription or recreational drug. In order to achieve the results a person initially felt when taking a drug, larger doses needed to be taken.

For example, a person may be taking prescribed medications to combat pain after surgery. As time passes, their body gets accustomed to the drug intake and numbs the pain less effectively than before. The drug effect weakens, and the only visible solution is to increase the dosage.

As higher doses are being taken, another physical occurrence takes place - drug dependence.

In most cases, one phenomenon leads to another where prolonged consumption persists. Tolerance and dependence are often linked together for that reason.

There is an exception when an addiction to a drug (e.g., cocaine) occurs over a short lapse of time and when taken repeatedly. A body's tolerance and urge for a higher dose are developed at a later stage.

Tolerance and dependence are also a part of the pathology of drug addiction and the first stage of its cycle (binge/intoxication).

Needless to say, drug tolerance leads to adverse side effects, one of them being a constant physical appetite to consume a higher dose of a drug. One of the consequences of indulging in drug abuse may be over dose.

Acute and Chronic Tolerance

The difference between acute and chronic tolerance is determined by how much time is needed to develop drug tolerance.

Acute tolerance to a drug occurs within a short period of time. Even one drinking session or a drug-taking episode is enough - opioids like heroin are a good example of this.

In contrast, chronic tolerance to a drug builds up throughout an extended period of time. It takes repeated drug abuse to develop a chronic tolerance. A person might have gone through an opioid treatment to relieve chronic noncancer pain that eventually led to drug dependence over time.

Is Drug Tolerance Genetic?

There are no genetic factors that prove drug tolerance is genetic. Some people may be predisposed to developing tolerance to a drug due to disorders. It can be related to liver or kidney disorders. Impaired metabolism prevents organs from properly processing the drug. The dosage level may vary as well as dose intervals and the onset of action after administration.

Dosage also varies based on a person's bodily makeup and mental health conditions. Drug-to-drug interactions are another factor that can alter the dosage.

Difference Between Tolerance and Dependence

Terms like "drug tolerance" and "drug dependence" are often confused. Sometimes "drug resistance" is misused, too. It is important to differentiate the terms as each of them have distinctive characteristics and describe unique conditions.

Although they lead to the same outcome, tolerance and dependence have distinguishable effects on the body. Drug resistance is what happens between the two conditions. Here is a detailed breakdown:


As the drug tolerance definition states, the phenomenon occurs due to extended drug consumption. Depending on a person's physique and mental health conditions, tolerance to a drug can take a short or long time to develop. Some people may be predisposed to developing drug tolerance faster due to various disorders.

Typically, tolerance is caused when the metabolism of a drug accelerates. The acceleration is caused by the stimulated activity of liver enzymes that are involved in metabolizing drugs. The drug attaches to cell receptors that can be decreased in number. Or the bond between drug and cell receptors weakens.

This is how metabolization looks:

There is a healthy number of receptors that play a role in metabolizing a drug. But for example,  if a person suffers from cocaine addiction, it overstimulates the postsynaptic membrane. It means receptors can't handle the amount of dopamine coming in.

It leads to the down-regulation of receptors (decreased number of receptors), and now more of the drug is needed to get the same effect.

Drug tolerance occurs when drug abuse overstimulates receptors, resulting in their down-regulation or a protective mechanism that reduces the number of membrane receptors.

The opposite process of developing drug tolerance happens with painkillers or other medications.

A person has a healthy number of pain receptors. When a painkiller is taken, the drug blocks pain receptors, and less pain is received. Just like with narcotics that overstimulate receptors, the body understands that something abnormal is happening.

Consequently, the body tries to figure out the problem and fix it by up-regulating pain receptors or increasing their number. More pain receptors equal more pain, and the obvious solution is to take more medication.

In one study, patients who have insomnia were administered a small dose of alprazolam for a short term. Over a week, patients developed drug tolerance which resulted in around a 40% decrease in drug efficiency.

In both scenarios, when a person stops taking the drug, over time, the receptors will go back to normal. It is important to note that due to the lack or abundance of receptors, a person will either feel awful (withdrawal syndrome) or may experience acute pain that was bearable before.


Drug resistance occurs when a drug has been taken for so long that certain microbes have mutated and evolved to be resistant to the effects.

A vivid example of drug resistance is E. coli bacteria which is less susceptible to antibiotics effects or cancer cells that may gain the ability to withstand chemotherapy drugs.

Certain medications were designed to kill the microbes - however, those are the microbes "of the past." As natural selection goes, weaker bacteria and viruses have been killed, but the fittest ones are now thriving.

Since the antibiotics haven't yet been adjusted, microbes have had plenty of time to mutate randomly and have acquired drug resistance.

Simply, drug resistance means certain medications aren't strong enough to treat diseases, letting microbes live and multiply.


Drug dependence is what comes after the body has started tolerating the drug. It doesn't happen overnight but over an extended period of time. Three factors are related to drug dependence:

  • Rate of exposure
  • Dose
  • Drug potency

The breakeven point is when a person cannot properly function without taking a prescription or recreational drug. Although a person feels a need (and not a want anymore) to take another dose, it is still a step behind addiction.

Being drug dependent isn't the same as being addicted - there are some distinctions - but when ignored, dependence may be developed into an addiction.

Drug dependence is both physical and psychological. Physical dependence is when a person's body is adapted to a drug, and any dosage reduction or sudden halt in the presence of the drug in the body results in withdrawal. Psychological dependence is when the brain feeds off a drug's psychoactive properties for recreational use, to numb pain, or to avoid withdrawal symptoms.

As tolerance reaches its peak and a person stops taking a drug (or just reduces the dose), they start to feel much worse than before. This is called withdrawal syndrome.

There aren't enough - or too many, as in the case of painkillers - receptors to metabolize a drug. The process of withdrawal is harsh on the body and mind and can cause many adverse and acute symptoms.

For example, withdrawal of antidepressants and drugs like benzodiazepines (BZ) may have life-threatening circumstances. For example, mild BZ withdrawal may have some of the following symptoms:

  • Anxiety
  • Dizziness
  • Apprehension
  • Headache
  • Weight loss
  • Light and sound intolerance
  • Hyperosmia (sensitivity to smells)

Acute withdrawal symptoms may occur in more serious cases:

  • Nausea
  • Vertigo
  • Tachycardia
  • Depression
  • Panic attacks
  • Hyperthermia


Addiction is a person's inability to control behavior, craving, and appetite for a drug and is the inability to analyze problems. Drug-addicted people also suffer from a dysfunctional emotional response.

Unlike the conditions described above, addiction is a neurological condition. It is a complex phenomenon that forces a person to take a drug compulsively.

In terms of prescription medications, it is vital to follow the doctor's recommendations and not take higher doses than recommended. The use of illegal drugs and binge drinking is another risk factor that may lead to substance use disorder.

Although there isn't any cure for addiction, it is a treatable condition. What makes addiction dangerous is the inability to stop taking drugs despite a person's desire to do that. That's why getting treatment is one of the successful methods of recovering.

Types of Tolerance

Drug tolerance is a condition distinct from resistance, dependence, and types of drug addiction. Looking into it deeper, tolerance can be divided into seven clinical types. Recognizing a person's type of tolerance helps identify the most efficient treatment.

Acute Tolerance

Acute tolerance to a drug happens when the brain and central nervous system have an immediate reaction to the drug. By reducing the number of receptors, the body tries to minimize the effects of the substance.

Acute tolerance is common for those who smoke or take hallucinogens (e.g., LSD, psilocybin mushrooms, ecstasy, etc.).

Behavioral Tolerance

Behavioral tolerance is clearly referring to the behavior of substance users. Often a heavy user may take full control of their behavior in certain situations. The brain is able to refocus in the event of an emergency, even when intoxicated.

One of the vivid examples is appearing sober when met with law enforcement. Once the "threat" is gone, so does the mirage of soberness.

Behavioral tolerance is the ability of the brain to adapt rapidly to extreme situations. Some brain areas seem to be unaffected or adapted to constant substance abuse.

Dispositional Tolerance

Dispositional drug tolerance refers to the inability of the brain to dispose of the substance on its own. Instead, the neurotransmitters and receptor sites are responsible for the process. However, certain drugs disrupt the process.

Consequently, a person's body is now responsible for the disposal of substances. The body does it by accelerating the metabolism and forcing blood to quickly circulate the substance and remove it through the liver.

The results of the drug are reduced, which means the current dose cannot give the same desired effect anymore.

Inverse Tolerance

Inverse tolerance to a drug is a confusing phenomenon that has two characteristics complicating the analysis. Inverse tolerance occurs in the brain and central nervous system and influences how the chemicals are processed.

The occurrence is often associated with the Kindling Effect. The term refers to sensitization or desensitization to a substance.

Sensitization is when a person with chronic substance abuse suffers from liver problems and the body's ability to process substances. In contrast, desensitization is when the effects of the chemical intensify.

Inverse tolerance complicates recovery and makes relapses harder. The withdrawal symptoms are more severe and last longer.

Pharmacodynamic Tolerance

Whenever a person takes a drug, the brain constantly tries to reduce the effect of the substance taken. Many parts of the brain - including nerve cells, receptors, reuptake, and the transition processes - work in unison to minimize the substance's influence on the body and mind. Your brain initiates a protective mechanism by either producing an antidote or increasing the number of receptors.

Reverse Tolerance

Reserve tolerance is often referred to as sensitization and grouped with inverse tolerance.

Reverse tolerance occurs when the body can no longer process the drug. Most drugs have to pass through the liver, and when the organ stops functioning properly, drug clearance worsens. As a result, a person's sensitivity to its effect is intensified.

Select Tolerance

Select tolerance is not fully understood, just like the inverse one. In simple terms, it happens when the brain reduces the substance's effect. Although the brain may not be able to entirely dull the effects of the drugs, a person will try to achieve the desired effect by doubling the dose.

While the brain tries to fight the drug, other organs (e.g., lungs, throat, cannabinoid receptors) are intoxicated by the substance.

Select tolerance is particularly dangerous when a person constantly increases the dose because the current dose no longer gives the same high effect.

Such tolerance develops towards a frequently abused drug such as heroin when an addict keeps consuming it but no longer feels the euphoria. In the meantime, the body suffers from the toxicity of a drug.

Besides the damage to the body, there is a risk of overdosing as an addict never stops seeking higher doses.

Drug Tolerance Risks

When taking a drug for an extended period of time, a person may develop drug tolerance. And this occurrence is harmful in several ways.

Adaptation to a Drug

Once the body adapts to a prescription or recreational drug, more often than not, a person tends to take a higher dose. An example can be a doctor prescribing a higher dosage of medication or a person mixing drugs and alcohol, or smoking an extra joint of cannabis.

Harmful Drug Dependence

Drug tolerance is often followed by drug dependence. Once the body and mind initiate the protective mechanism and reduce the effects of a drug - dependence occurs. Drug dependence influences the physiology and psychology of a person. A person's body refuses to function properly without a boost of drugs.

Drug consumption lets a person avoid horrible withdrawal symptoms, but the craving never goes away. Moreover, to kill the pain or receive the desired amount of dopamine, the last dose should be increased.

Preventable Addiction

If dependence gets out of hand, a person is likely to become addicted to a drug. Often an addict will irrationally seek the drug and increase the dosage with every consumption. Or turn to more potent drugs off the streets.

Increased Risk of Overdose

Once a person's body and mind adapt to the drug, the brain never stops blocking the substance's effects (although it doesn't mean the brain is not being damaged in the meantime).

This is the reason why so many addicts keep looking for a better and stronger high - their brain doesn't let them or is no longer able to process drugs fully.

This is a grave issue because addicts may not feel intoxicated - however, their bodies do. While an addict consumes illegal drugs, they inflict fatal damage to the organs.

In addition to that, drug addiction makes people seek irrational ways to find the source of dopamine. It can be through mixing up narcotics or experimenting with unknown substances. All of it may lead to dire consequences, including drug overdose.

Chronic Pain and Mental Health Problems

Frequent drug abuse takes a toll on the mind and body. The body fails to metabolize a large amount of substance, and the brain gets used to the addictive surge of dopamine.

The lack of dopamine may lead to common mental problems such as depression, anxiety, fearfulness, and other conditions.

The more a person feeds their body with the substance, the more harm is being inflicted. Since most drugs are cleared out through the liver, there is an increased risk of liver failure.

As a person suddenly isolates oneself from drugs, withdrawal begins with its symptoms and such possible serious consequences as sweating, muscle aches, anxiety, etc.

How to Minimize and Prevent Drug Tolerance

There are measures that can be taken to prevent tolerance. The same recommendations may be given to people who already experience tolerance and are afraid of its further development.

To avoid drug tolerance or reduce its risks, a person can:

  • Consult your doctor about non-pharmaceutical treatment: Although not always possible or available, it is worth giving a non-pharmaceutical treatment a shot. Your doctor may find an alternative solution to your problem that would have fewer side effects yet is no less effective.
  • Throw away unused prescriptions: The unused medication that is no longer consumed can be disposed of. This will prevent a person from taking the medication without a doctor's prescription.
  • Start a (recovery) journal: If you take prescription medications, it is advised to keep a journal. Tracking the dosage, symptoms, and drug's effects is necessary to monitor (and perhaps predict) drug tolerance.
  • Regular doctor's visits: Doctors may identify drug tolerance at an early stage based on your drug usage and its efficacy. If a drug no longer provides the desired effect, it is necessary to inform your healthcare provider.
  • Do not increase drug dosage: Self-treatment can be quite dangerous when it comes to potent medications. Keep taking the prescribed dose of the same drug without making any changes to your routine. Next, consult with your doctor to discuss the issue.
  • Seek help: In case of developed drug tolerance, seeking help from a substance addiction treatment program is advised.


Drug tolerance is developed to any kind of drug that has been used for an extended period. The substance can be alcohol, prescription medications, or recreational drugs.

When the substance is first introduced to the body, it is regarded as a foreign substance, and your body treats it as a threat. Over time, the brain adapts to the effect of a drug and starts tolerating it. In short, your body and mind adapt to the drug, and the current dose is no longer as efficient as it was before.

Drug tolerance often leads to drug dependence when the body cannot function properly without the substance. The body and brain are adjusted to the drug and require its therapeutic or psychoactive properties.

Developing drug tolerance and dependency forces a person to continue taking the drug. Otherwise, there is a risk of experiencing withdrawal symptoms. A higher dose or a longer drinking session seems like a much-needed cure for the moment, but it can soon grow into an addiction where a treatment program like the one we offer at Miracles Asia is needed to avoid health issues.

Predicting and preventing drug tolerance is no easy task. But if you are about to start potent medication, there are measures you can take to minimize the risks.

Frequently Asked Questions

Is it possible to predict drug tolerance?

It's almost impossible to predict drug tolerance, especially to prevent it from occurring if you are prescribed to consume strong medications.

You can start a diary, ask your doctor for alternative solutions, and follow the healthcare provider's instructions on how to use a drug effectively.

If you feel any changes and notice the drug has become less effective, you should consult your doctor as soon as possible.

What is the biggest risk of drug tolerance?

The biggest risk of drug tolerance is the need to increase the drug's dose. This is because the body gets used to the substance over time and provides weaker results.

Those who suffer chronic pain may be at risk of misusing their medications.

What other factors influence drug tolerance?

Despite drugs being the biggest factor influencing the body's tolerance, your physique, age, and health conditions have an impact, too.

What is the most effective way to treat drug tolerance?

Abstaining from drug consumption is the most effective method to treat drug tolerance. However, it may result in withdrawal symptoms that can be mild or serious.

Your doctor may recommend taking a smaller dose and gradually reducing it over time. An alternative medication may be given to alleviate the symptoms.

Article by
Catherine O'Leary
Catherine is a trained mental health and addiction professional, with over 35 years’ experience in health care and addiction recovery. She has successfully completed a Certificate of Nursing, Bachelor of Nursing, Master of Arts (health), Graduate Diploma of Advanced Psychiatric Nursing, Certificate of Drug and Alcohol Nursing, Mental Health First Aid Instructor Certification and a Diploma of Counselling.
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