What Does Drug Tolerance Mean, and When Should You Worry?

And How It's Different From Addiction and Drug Dependence

By Anna Giorgi 

Published on June 28, 2022

 Medically reviewed by Erika Prouty, PharmD

If you use a drug repeatedly, your body can develop drug tolerance. With this condition, you have to take higher doses of the drug—or change to a different drug—to get the same benefit or effect you had when you first began using it.

You can develop a drug tolerance to any drug, regardless of its purpose. It's possible to form a drug tolerance to prescription morphine you take for pain relief or recreational drugs like cocaine.

While drug tolerance can be a challenge, solutions are available. Your healthcare provider can conduct regular exams to reevaluate your treatment plan and reduce the incidence of drug tolerance. Your provider also can decide whether you may benefit from a higher dose of the drug or a new medication to offset your drug tolerance.

This article compares drug tolerance, addiction, and dependence and discusses various types of tolerance and associated drug types.



Drug Tolerance: Not Addiction or Dependence

Drug tolerance can be easily confused with drug addiction (also referred to as substance use disorder) or drug dependence. While drug tolerance can occur with either condition, it can also exist as a separate condition.

Key Differences

Here are the key differences among drug tolerance, addiction, and dependence that define these conditions:

Drug tolerance naturally occurs when your body has a reduced response to a drug that is used often. You can develop a high tolerance if you take a substance or drug regularly. It can also occur as a result of genetics.

Characteristics of drug tolerance include:1

  • A feeling that the drug stopped working after continued use over time

  • The need for larger doses of a drug to achieve the same effect

  • The need to stop the drug, then reintroduce it to reestablish efficacy

  • Developing a tolerance to other drugs in the same class

  • A higher risk of addiction when a drug is used in larger doses

Drug addiction, also called substance use disorder, is a chronic brain disorder and mental illness. It involves the compulsive use of alcohol, recreational drugs, or prescription medicines, despite the negative outcomes caused by the use and overuse of the drug.

Characteristics of addiction include:

  • Occurrence with or without drug dependency

  • Prioritizing the possession and use of the drug over physical needs, relationships, and work

  • Changes in your brain that interfere with normal judgment, learning, and behavior

  • The onset of cravings or severe symptoms during withdrawal, when you stop using the drug

  • Inability to control or reduce the use of the drug

  • Increasing drug tolerance as your body adjusts to the drug's constant presence

Drug dependence is a physical dependence that occurs when your body adjusts to the constant presence of a particular drug in your system and accepts it as a new normal. While there is a difference between addiction and dependence, addiction often follows dependence.

Characteristics of drug dependence include:1

  • Physical changes in your body that make it adapt to having a particular drug in your system

  • A physical need to have the drug in your system to function normally

  • The onset of withdrawal symptoms when attempting to stop or lower the dosage of the drug

  • Often accompanied by tolerance as your body accepts the drug and its effect lessens

 Substance Use Disorder & Addiction

Lists of Drugs Known to Change Tolerance Levels

The possibility of developing tolerance to a specific drug varies by individual and the type of drug taken. The following drugs are known to change tolerance levels:

  • Alcohol2

  • Allergy drugs3

  • Long-acting beta-agonists

  • Antidepressants:4

  • Monoamine oxidase inhibitors (MAOIs)

  • Serotonin reuptake inhibitors (SSRIs)

  • Antidiabetics5

  • Antihistamines6

  • Anxiolytics (antianxiety drugs)7

  • Benzodiazepines 

  • Cancer drugs8

  • Cardiac medications9

  • Nitrates10

  • Corticosteroids5

  • Hallucinogens5

  • Opioids5

 What Is Opioid Use Disorder?

Theories About the Cause of Drug Tolerance

While drug tolerance occurs commonly with the long-term use of certain substances, the causes of this problem aren't well understood. When used as prescribed, drug tolerance is unknown.

Some people may have a natural tolerance to certain drugs or drug types as a result of genetics. However, it's unclear why others develop an acquired drug tolerance. There are several theories about the cause of acquired drug tolerance


There may be a psychological element to drug tolerance. External factors, such as stress, that impact your psychological condition, can contribute to drug tolerance. Stress interferes with a drug's ability to bind to plasma and tissue proteins, which is necessary for efficacy.11


Behavioral tolerance suggests that you become conditioned to the effect of a psychoactive drug over time. As a result, you develop behaviors to overcome the drug's effects.


The pharmacodynamic theory of drug tolerance says that the condition occurs as the body works to adapt to the presence of a foreign substance.12

As you take a drug for longer periods of time, the receptors or enzymes in your brain and body become desensitized to the drug. This makes it less effective in the same amounts. As a result, your body needs a higher dose to achieve the desired effect of the drug.


Metabolic tolerance results from a faster-than-normal elimination of a drug from your body. It is linked with a specific group of liver enzymes that metabolize alcohol after chronic drinking.

The effect lowers the concentration of blood alcohol and lessens the time during which alcohol remains active in your body. This reduces the amount of time you are subject to the intoxicating effects of alcohol.13


Reverse tolerance, also called sensitization, has the opposite effect of other types of tolerance. It occurs with drugs like psychoactive substances. Repeated use of the drug changes the body's sensitivity to it so that repeated use of the drug enhances, rather than reduces, its effect.14


Drug tolerance interferes with a drug's ability to deliver the intended benefit or effect. However, it also poses several potential problems that can lead to serious results.

If you continue to take a drug despite having signs of tolerance, you increase your risk of the following dangers:2

  • Increasing side effects by taking the drug in higher doses than intended

  • Relapse or worsening of pain or a medical condition previously controlled by the drug

  • Development of a substance use disorder, particularly of opioids, if you increase doses without medical advice

  • Cross-tolerance to other drugs in the same group

  • A higher risk of drug dependence, addiction, and overdose for certain classes of drugs

 How Does Cancer Become Resistant to Chemotherapy?

How to Minimize the Risks of Drug Tolerance

While it's not possible to predict or prevent drug tolerance, you can work to reduce the risks of this condition by taking these steps:

  • Keep a journal to track the effects of any long-term medicines that you take.

  • Keep appointments with your healthcare provider so they can monitor your medication usage and efficacy.

  • Contact your healthcare provider immediately if you notice that your medicine has become less effective.

  • Don't stop taking your medicine or change the dose without advice from your healthcare provider.

  • Carefully administer new dosage amounts to prevent overdose (if lowering a dose, be careful not to go too low, too fast, as this can cause withdrawal symptoms).

  • Seek a substance abuse treatment program if you notice drug tolerance to alcohol and/or recreational drugs.

If you suspect that you have a drug tolerance, your healthcare provider will evaluate your treatment plan to determine changes in dosage or the need for different medications.

Dangers of Drug Tolerance

Drug tolerance increases your risk of dependence, addiction, and overdose since your body reacts to normal doses differently. Never change the dose of a prescribed medication without advice from your healthcare provider.


You can have a drug tolerance to a drug that you often take for a long time. This can occur with alcohol and both prescribed and recreational drugs.

The problem develops when your body becomes familiar with the drug and no longer regards it as a foreign substance. Instead, the drug is treated as part of your body's system. This makes it less useful for the pain or chronic illness it treats.

Your healthcare provider can change your treatment plan to offset the effects of drug tolerance. Methods like raising the drug dose, using a new drug, stopping the drug for a short time, or finding nonmedical treatments, may work for you.